Publications

Stem cell hypertranscription

Publications_Index
Alpha satellite RNA marks the perinucleolar compartment and represses ribosomal RNA expression in naïve human embryonic stem cells

Authors: Mittal K, Ataei L, Ramalho-Santos M.

Reference: bioRxiv, 2025.07.11.664446; doi: 10.1101/2025.07.11.664446

20 years of stemness: From stem cells to hypertranscription and back

Authors: Kim YK, Ramalho-Santos M.
Reference: Stem Cell Reports, 2025 Mar 11;20(3):102406. doi: /10.1016/j.stemcr.2025.102406
PMID: 39919752

LINE1 elements at distal junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells

Authors: Ataei L, Zhang J, Monis S, Giemza K, Mittal K, Yang J, Shimomura M, McStay B, Wilson MD, Ramalho-Santos M.
Reference: Genes Dev, 2025 Feb 3;39(3-4):280-298. doi: 10.1101/gad.351979.124
PMID: 39797762

Hypertranscription: the invisible hand in stem cell biology

Authors: Kim YK, Collignon E, Martin SB, Ramalho-Santos M.

Reference: Trends in Genetics, 2024, https://doi.org/10.1016/j.tig.2024.08.005

m6A RNA methylation orchestrates transcriptional dormancy during paused pluripotency

Authors: Collignon E, Cho B, Furlan G, Fothergill-Robinson J, Martin SB, McClymont SA, Ross RL, Limbach PA, Ramalho-Santos M.

Reference: Nature Cell Biology, 2023, https://doi.org/10.1038/s41556-023-01212-x

Absolute scaling of single-cell transcriptomes identifies pervasive hypertranscription in adult stem and progenitor cells

Authors: Kim YK, Cho B, Cook DP, Trcka D, Wrana JL, Ramalho-Santos M.

Reference: Cell Reports, 2023, https://www.cell.com/cell-reports/fulltext/S2211-1247(22)01882-4

Regulation, functions and transmission of bivalent chromatin during mammalian development

Authors: Macrae TA, Fothergill-Robinson J, Ramalho-Santos M.

Reference: Nat Rev Mol Cell Bio, https://doi.org/10.1038/s41580-022-00518-2

Chd1 regulates repair of promoter-proximal DNA breaks to sustain hypertranscription in embryonic stem cells

Authors: Bulut-Karslioglu A, Jin H, Kim YK, Cho B, Guzman-Ayala M, JK Williamson A, Hejna M, Stötzel M, Whetton AD, S. Song J, Ramalho-Santos M

Reference: Nature Communications, 2021 Aug 11;12(1):4859.

The deubiquitinase Usp9x regulates PRC2-mediated chromatin reprogramming during mouse development

Authors: Macrae TA, Ramalho-Santos M.

Reference: Nature Communications. 2021 Mar 25;12(1):1865.

PMID: 33767158

The Transcriptionally Permissive Chromatin State of Embryonic Stem Cells Is Acutely Tuned to Translational Output.

Authors: Bulut-Karslioglu A, Macrae TA, Oses-Prieto JA, Covarrubias S, Percharde M, Ku G, Diaz A, McManus MT, Burlingame AL, Ramalho-Santos M.
Reference: Cell Stem Cell. 2018 Mar 1;22(3):369-383.e8. doi: 10.1016/j.stem.2018.02.004.
PMID: 29499153

Global Hypertranscription in the Mouse Embryonic Germline

Authors: Percharde M, Wong P, Ramalho-Santos M.
Reference: Cell Rep. 2017 Jun 6;19(10):1987-1996. doi: 10.1016/j.celrep.2017.05.036.
PMID: 28591571

Hypertranscription in Development, Stem Cells, and Regeneration.

Authors: Percharde M, Bulut-Karslioglu A, Ramalho-Santos M.
Reference: Dev Cell. 2017 Jan 9;40(1):9-21. doi: 10.1016/j.devcel.2016.11.010. Epub 2016 Dec 15. Review.
PMID: 27989554

Emergence of hematopoietic stem and progenitor cells involves a Chd1-dependent increase in total nascent transcription.

Authors: Koh FM, Lizama CO, Wong P, Hawkins JS, Zovein AC, Ramalho-Santos M.
Reference: Proc Natl Acad Sci U S A. 2015 Apr 7;112(14):E1734-43. doi: 10.1073/pnas.1424850112. Epub 2015 Mar 23.
PMID: 25831528

Chd1 is essential for the high transcriptional output and rapid growth of the mouse epiblast.

Authors: Guzman-Ayala M, Sachs M, Koh FM, Onodera C, Bulut-Karslioglu A, Lin CJ, Wong P, Nitta R, Song JS, Ramalho-Santos M.
Reference: Development. 2015 Jan 1;142(1):118-27. doi: 10.1242/dev.114843. Epub 2014 Dec 5.
PMID: 25480920

Hira-mediated H3.3 incorporation is required for DNA replication and ribosomal RNA transcription in the mouse zygote.

Authors: Lin CJ, Koh FM, Wong P, Conti M, Ramalho-Santos M.
Reference: Dev Cell. 2014 Aug 11;30(3):268-79. doi: 10.1016/j.devcel.2014.06.022. Epub 2014 Jul 31.
PMID: 25087892

Bivalent chromatin marks developmental regulatory genes in the mouse embryonic germline in vivo.

Authors: Sachs M, Onodera C, Blaschke K, Ebata KT, Song JS, Ramalho-Santos M.
Reference: Cell Rep. 2013 Jun 27;3(6):1777-84. doi: 10.1016/j.celrep.2013.04.032. Epub 2013 May 30.
PMID: 23727241

Open chromatin in pluripotency and reprogramming.

Authors: Gaspar-Maia A, Alajem A, Meshorer E, Ramalho-Santos M.
Reference: Nat Rev Mol Cell Biol. 2011 Jan;12(1):36-47. doi: 10.1038/nrm3036. Review. Erratum in: Nat Rev Mol Cell Biol. 2011 Apr;12(4):273.
PMID: 21179060

Parallel gateways to pluripotency: open chromatin in stem cells and development.

Authors: Koh FM, Sachs M, Guzman-Ayala M, Ramalho-Santos M.
Reference: Curr Opin Genet Dev. 2010 Oct;20(5):492-9. doi: 10.1016/j.gde.2010.06.002. Epub 2010 Jul 2. Review.
PMID: 20598875

Chd1 regulates open chromatin and pluripotency of embryonic stem cells.

Authors: Gaspar-Maia A, Alajem A, Polesso F, Sridharan R, Mason MJ, Heidersbach A, Ramalho-Santos J, McManus MT, Plath K, Meshorer E, Ramalho-Santos M.
Reference: Nature. 2009 Aug 13;460(7257):863-8. doi: 10.1038/nature08212. Epub 2009 Jul 8.
PMID: 19587682

Stem cells as probabilistic self-producing entities.

Authors: Ramalho-Santos M.
Reference: Bioessays. 2004 Sep;26(9):1013-6.
PMID: 15351971

"Stemness": transcriptional profiling of embryonic and adult stem cells.

Authors: Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA.
Reference: Science. 2002 Oct 18;298(5593):597-600. Epub 2002 Sep 12.
PMID: 12228720

Developmental pausing

Publications_Index
Hypertranscription: the invisible hand in stem cell biology

Authors: Kim YK, Collignon E, Martin SB, Ramalho-Santos M.

Reference: Trends in Genetics, 2024, https://doi.org/10.1016/j.tig.2024.08.005

m6A RNA methylation orchestrates transcriptional dormancy during paused pluripotency

Authors: Collignon E, Cho B, Furlan G, Fothergill-Robinson J, Martin SB, McClymont SA, Ross RL, Limbach PA, Ramalho-Santos M.

Reference: Nature Cell Biology, 2023, https://doi.org/10.1038/s41556-023-01212-x

Colorectal Cancer Cells Enter a Diapause-like DTP State to Survive Chemotherapy

Authors: Rehman AK, Haynes J, Collignon E, Brown KR, Wang Y, Nixon AML, Bruce JP, Wintersinger JA, Mer AS, Lo EBL, Leung C, Lima-Fernandes E, Pedley NM, Soares F, McGibbon S, He HH, Pollet A, Pugh TJ, Haibe-Kains B, Morris Q, Ramalho-Santos M, Goyal S, Moffat J, O'Brien CA

Reference :Cell. 2021 Jan 7; 184(1):226-242.

PMID: 33417860

The Transcriptionally Permissive Chromatin State of Embryonic Stem Cells Is Acutely Tuned to Translational Output.

Authors: Bulut-Karslioglu A, Macrae TA, Oses-Prieto JA, Covarrubias S, Percharde M, Ku G, Diaz A, McManus MT, Burlingame AL, Ramalho-Santos M.
Reference: Cell Stem Cell. 2018 Mar 1;22(3):369-383.e8. doi: 10.1016/j.stem.2018.02.004.
PMID: 29499153

Inhibition of mTOR induces a paused pluripotent state.

Authors: Bulut-Karslioglu A, Biechele S, Jin H, Macrae TA, Hejna M, Gertsenstein M, Song JS, Ramalho-Santos M.
Reference: Nature. 2016 Dec 1;540(7631):119-123. doi: 10.1038/nature20578. Epub 2016 Nov 23.
PMID: 27880763

Transposons in development

Publications_Index
Alpha satellite RNA marks the perinucleolar compartment and represses ribosomal RNA expression in naïve human embryonic stem cells

Authors: Mittal K, Ataei L, Ramalho-Santos M.

Reference: bioRxiv, 2025.07.11.664446; doi: 10.1101/2025.07.11.664446

LINE1 elements at distal junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells

Authors: Ataei L, Zhang J, Monis S, Giemza K, Mittal K, Yang J, Shimomura M, McStay B, Wilson MD, Ramalho-Santos M.
Reference: Genes Dev, 2025 Feb 3;39(3-4):280-298. doi: 10.1101/gad.351979.124
PMID: 39797762

LINE1 and PRC2 control nucleolar organization and repression of the 8C state in human ESCs

Authors: Zhang J, Ataei L, Mittal K, Wu L, Caldwell L, Huynh L, Sarajideen S, Tse K, Simon MM, Mazid A, Cook DP, Trcka D, Kwan T, Hoffman MM, Wrana JL, Esteban MA, Ramalho-Santos M.

Reference: Developmental Cell, 2024. https://doi.org/10.1016/j.devcel.2024.09.024

Depletion of nuclear LINE1 RNA in mouse ESCs and embryos

Authors: Percharde M, Lin CJ, Ramalho-Santos M.

Reference: STAR Protoc, 2021 Aug 9;2(3):100726. doi: 10.1016/j.xpro.2021.100726

PMID: 34409306

Homotypic clustering of L1 and B1/Alu repeats compartmentalizes the 3D genome

Authors: Lu JY, Chang L, Li T, Wang T, Yin Y, Zhan G, Han X, Zhang K, Tao Y, Percharde M, Wang L, Peng Q, Yan P, Zhang H, Bi X, Shao W, Hong Y, Wu Z, Ma R, Wang P, Li W, Zhang J, Chang Z, Hou Y, Zhu B, Santos MR, Li P, Xie W, Na J, Sun Y, Shen X.

Reference : Cell Research. 2021 Jan 29, 10.1038/s41422-020-00466-6

PMID: 33514913

Genomic Repeats Categorize Genes with Distinct Functions for Orchestrated Regulation

Authors: Lu JY, Shao W, Chang L, Yin Y, Li T, Zhang H, Hong Y, Percharde M, Guo L, Wu Z, Liu L, Liu W, Yan P, Ramalho-Santos M, Sun Y, Shen X.

Reference: Cell Rep. 2020 Mar 10; 30 (10) :3296-3311
PMID: 32160538

What Doesn’t Kill You Makes You Stronger: Transposons as Dual Players in Chromatin Regulation and Genomic Variation

Authors: Percharde M, Sultana T, Ramalho-Santos M.
Reference: Bioessays. 2020 Feb 13. https://onlinelibrary.wiley.com/doi/full/10.1002/bies.201900232
PMID: 32053231

 

A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity.

Authors: Percharde M, Lin CJ, Yin Y, Guan J, Peixoto GA, Bulut-Karslioglu A, Biechele S, Huang B, Shen X, Ramalho-Santos M.
Reference: Cell. 2018 Jun 19. pii: S0092-8674(18)30655-X. doi: 10.1016/j.cell.2018.05.043.
PMID: 29937225

Environment-epigenome-development

Publications_Index
Sex-specific epigenetic profile of inner cell mass of mice conceived in vivo or by IVF

Authors: Ruggeri E, Lira-Albarrán S, Grow EJ, Liu X, Harner R, Maltepe E, Ramalho-Santos M, Donjacour A, Rinaudo P.
Reference: Mol Hum Reprod. 2020 Nov 1;26(11):866-878. doi: 10.1093/molehr/gaaa064.
PMID: 33010164

Maternal vitamin C regulates reprogramming of DNA methylation and germline development

Authors: DiTroia SP, Percharde M, Guerquin MJ, Wall E, Collignon E, Ebata KT, Mesh K, Mahesula S, Agathocleous M, Laird DJ, Livera G, Ramalho-Santos M.
Reference: Nature. 2019 Sep 04. https://doi.org/10.1038/s41586-019-1536-1
PMID: 31719689

Vitamin C induces specific demethylation of H3K9me2 in mouse embryonic stem cells via Kdm3a/b.

Authors: Ebata KT, Mesh K, Liu S, Bilenky M, Fekete A, Acker MG, Hirst M, Garcia BA, Ramalho-Santos M.
Reference: Epigenetics Chromatin. 2017 Jul 12;10:36. doi: 10.1186/s13072-017-0143-3. eCollection 2017.
PMID: 28706564

Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells.

Authors: Blaschke K, Ebata KT, Karimi MM, Zepeda-Martínez JA, Goyal P, Mahapatra S, Tam A, Laird DJ, Hirst M, Rao A, Lorincz MC, Ramalho-Santos M.
Reference: Nature. 2013 Aug 8;500(7461):222-6. doi: 10.1038/nature12362. Epub 2013 Jun 30.
PMID: 23812591

Others

Publications_Index
The deubiquitinase Usp9x regulates PRC2-mediated chromatin reprogramming during mouse development

Authors: Macrae TA, Ramalho-Santos M.

Reference: Nature Communications. 2021 Mar 25;12(1):1865.

PMID: 33767158

Tet2 Rescues Age-Related Regenerative Decline and Enhances Cognitive Function in the Adult Mouse Brain.

Authors: Gontier G, Iyer M, Shea JM, Bieri G, Wheatley EG, Ramalho-Santos M, Villeda SA.
Reference: Cell Rep. 2018 Feb 20;22(8):1974-1981. doi: 10.1016/j.celrep.2018.02.001.
PMID: 29466726

CHD1 loss sensitizes prostate cancer to DNA damaging therapy by promoting error-prone double-strand break repair

Authors: Shenoy TR, Boysen G, Wang MY, Xu QZ, Guo W, Koh FM, Wang C, Zhang LZ, Wang Y, Gil V, Aziz S, Christova R, Rodrigues DN, Crespo M, Rescigno P, Tunariu N, Riisnaes R, Zafeiriou Z, Flohr P, Yuan W, Knight E, Swain A, Ramalho-Santos M, Xu DY, de Bono J, Wu H.
Reference: Ann Oncol. 2017 Jul 1;28(7):1495-1507. doi: 10.1093/annonc/mdx165.
PMID: 28383660

Unwind and transcribe: chromatin reprogramming in the early mammalian embryo.

Authors: Biechele S, Lin CJ, Rinaudo PF, Ramalho-Santos M.
Reference: Curr Opin Genet Dev. 2015 Oct;34:17-23. doi: 10.1016/j.gde.2015.06.003. Epub 2015 Jul 13. Review.
PMID: 26183187 

HiTSelect: a comprehensive tool for high-complexity-pooled screen analysis.

Authors: Diaz AA, Qin H, Ramalho-Santos M, Song JS.
Reference: Nucleic Acids Res. 2015 Feb 18;43(3):e16. doi: 10.1093/nar/gku1197. Epub 2014 Nov 26.
PMID: 25428347

A comparative encyclopedia of DNA elements in the mouse genome.

‍ ‍

Authors: Yue F, Cheng Y, Breschi A, et al.
Reference: Nature. 2014 Nov 20;515(7527):355-64. doi: 10.1038/nature13992.
PMID: 25409824

‍ ‍

Systematic identification of barriers to human iPSC generation.

Authors: Qin H, Diaz A, Blouin L, Lebbink RJ, Patena W, Tanbun P, LeProust EM, McManus MT, Song JS, Ramalho-Santos M.
Reference: Cell. 2014 Jul 17;158(2):449-461. doi: 10.1016/j.cell.2014.05.040.
PMID: 25036638

Somatic cells regulate maternal mRNA translation and developmental competence of mouse oocytes.

Authors: Chen J, Torcia S, Xie F, Lin CJ, Cakmak H, Franciosi F, Horner K, Onodera C, Song JS, Cedars MI, Ramalho-Santos M, Conti M.
Reference: Nat Cell Biol. 2013 Dec;15(12):1415-23. doi: 10.1038/ncb2873. Epub 2013 Nov 24.
PMID: 24270888 

Histone variant H3.3 maintains a decondensed chromatin state essential for mouse preimplantation development.

Authors: Lin CJ, Conti M, Ramalho-Santos M.
Reference: Development. 2013 Sep;140(17):3624-34. doi: 10.1242/dev.095513. Epub 2013 Jul 31.
PMID: 23903189

Smad2 is essential for maintenance of the human and mouse primed pluripotent stem cell state.

Authors: Sakaki-Yumoto M, Liu J, Ramalho-Santos M, Yoshida N, Derynck R.
Reference: J Biol Chem. 2013 Jun 21;288(25):18546-60. doi: 10.1074/jbc.M112.446591. Epub 2013 May 6.
PMID: 23649632

Transcriptional analysis of pluripotency reveals the Hippo pathway as a barrier to reprogramming.

Authors: Qin H, Blaschke K, Wei G, Ohi Y, Blouin L, Qi Z, Yu J, Yeh RF, Hebrok M, Ramalho-Santos M.
Reference: Hum Mol Genet. 2012 May 1;21(9):2054-67. doi: 10.1093/hmg/dds023. Epub 2012 Jan 27.
PMID: 22286172

Polycomb-like 3 promotes polycomb repressive complex 2 binding to CpG islands and embryonic stem cell self-renewal.

Authors: Hunkapiller J, Shen Y, Diaz A, Cagney G, McCleary D, Ramalho-Santos M, Krogan N, Ren B, Song JS, Reiter JF.
Reference: PLoS Genet. 2012;8(3):e1002576. doi: 10.1371/journal.pgen.1002576. Epub 2012 Mar 15.
PMID: 22438827

Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells.

Authors: Ohi Y, Qin H, Hong C, Blouin L, Polo JM, Guo T, Qi Z, Downey SL, Manos PD, Rossi DJ, Yu J, Hebrok M, Hochedlinger K, Costello JF, Song JS, Ramalho-Santos M.
Reference: Nat Cell Biol. 2011 May;13(5):541-9. doi: 10.1038/ncb2239. Epub 2011 Apr 17.
PMID: 21499256

Parallel gateways to pluripotency: open chromatin in stem cells and development.

Authors: Koh FM, Sachs M, Guzman-Ayala M, Ramalho-Santos M.
Reference: Curr Opin Genet Dev. 2010 Oct;20(5):492-9. doi: 10.1016/j.gde.2010.06.002. Epub 2010 Jul 2. Review.
PMID: 20598875

iPS cells: insights into basic biology.

Authors: Ramalho-Santos M.
Reference: Cell. 2009 Aug 21;138(4):616-8. doi: 10.1016/j.cell.2009.08.012.
PMID: 19703387

CompMoby: comparative MobyDick for detection of cis-regulatory motifs.

Authors: Chaivorapol C, Melton C, Wei G, Yeh RF, Ramalho-Santos M, Blelloch R, Li H.
Reference: BMC Bioinformatics. 2008 Oct 27;9:455. doi: 10.1186/1471-2105-9-455.
PMID: 18950538

The pluripotent transcriptome.

Authros: Grskovic M, Ramalho-Santos M.
Reference: StemBook [Internet]. Cambridge (MA): Harvard Stem Cell Institute; 2008-. 2008 Oct 10.
PMID: 20614622

High-efficiency stem cell fusion-mediated assay reveals Sall4 as an enhancer of reprogramming.

Authors: Wong CC, Gaspar-Maia A, Ramalho-Santos M, Reijo Pera RA.
Reference: PLoS One. 2008 Apr 16;3(4):e1955. doi: 10.1371/journal.pone.0001955.
PMID: 18414659

Generation of induced pluripotent stem cells in the absence of drug selection.

Authors: Blelloch R, Venere M, Yen J, Ramalho-Santos M.
Reference: Cell Stem Cell. 2007 Sep 13;1(3):245-7. doi: 10.1016/j.stem.2007.08.008. Epub 2007 Sep 6. No abstract available.
PMID: 18371358

Systematic identification of cis-regulatory sequences active in mouse and human embryonic stem cells.

Authors: Grskovic M, Chaivorapol C, Gaspar-Maia A, Li H, Ramalho-Santos M.
Reference: PLoS Genet. 2007 Aug;3(8):e145.
PMID: 17784790

On the origin of the term "stem cell".

Authors: Ramalho-Santos M, Willenbring H.
Reference: Cell Stem Cell. 2007 Jun 7;1(1):35-8. doi: 10.1016/j.stem.2007.05.013.
PMID: 18371332

RNA interference in embryonic stem cells and the prospects for future therapies.

Authors: Heidersbach A, Gaspar-Maia A, McManus MT, Ramalho-Santos M.
Reference: Gene Ther. 2006 Mar;13(6):478-86. Review.
PMID: 16520820

Stem cells as probabilistic self-producing entities.

Authors: Ramalho-Santos M.
Reference: Bioessays. 2004 Sep;26(9):1013-6.
PMID: 15351971

"Stemness": transcriptional profiling of embryonic and adult stem cells.

Authors: Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA.
Reference: Science. 2002 Oct 18;298(5593):597-600. Epub 2002 Sep 12.
PMID: 12228720

Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R symmetry by the mouse node.

Authors: Zhang XM, Ramalho-Santos M, McMahon AP.
Reference: Cell. 2001 Jul 27;106(2):781-92.
PMID: 11517919

Hedgehog signals regulate multiple aspects of gastrointestinal development.

Authors: Ramalho-Santos M, Melton DA, McMahon AP.
Reference: Development. 2000 Jun;127(12):2763-72.
PMID: 10821773

Will cell alliance breed bureaucracy and leave contributors out?

Authors: Haggarty SJ, Ramalho-Santos M.
Reference: Nature. 2000 Feb 10;403(6770):591. No abstract available.
PMID: 10688171

Cloning and characterization of cDNA encoding cardosin A, an RGD-containing plant aspartic proteinase.

Authors: Faro C, Ramalho-Santos M, Vieira M, Mendes A, Simões I, Andrade R, Veríssimo P, Lin X, Tang J, Pires E.
Reference: J Biol Chem. 1999 Oct 1;274(40):28724-9.
PMID: 10497243

Identification and proteolytic processing of procardosin A.

Authors: Ramalho-Santos M, Veríssimo P, Cortes L, Samyn B, Van Beeumen J, Pires E, Faro C.
Reference: Eur J Biochem. 1998 Jul 1;255(1):133-8.
PMID: 9692911

Cardosinogen A. The precursor form of the major aspartic proteinase from cardoon.

Authors: Ramalho-Santos M, Pissarra J, Pires E, Faro C.
Reference: Adv Exp Med Biol. 1998;436:253-8. No abstract available.
PMID: 9561227

 

2025

Featured
Nodal/Smad2 signaling sustains developmental pausing by repressing Pparg-mediated lipid metabolism
Nodal/Smad2 signaling sustains developmental pausing by repressing Pparg-mediated lipid metabolism

Authors: Furlan G, Martin SB, Cho B, McClymont SA, Robertson EJ, Colligon E, Ramalho-Santos M.

Reference: bioRxiv, 2025.09.08.674904; doi: 10.1101/2025.09.08.674904

CHD1 is a synthetic lethal vulnerability in MYC-driven breast cancer
CHD1 is a synthetic lethal vulnerability in MYC-driven breast cancer

Authors: Cho B, Furlan G, Lin P, Shen M, Mittal K, Mazzanti A, Penn L, Ramalho-Santos M.

Reference: bioRxiv, 2025.08.14.670376; doi: 10.1101/2025.08.14.670376

Alpha satellite RNA marks the perinucleolar compartment and represses ribosomal RNA expression in naïve human embryonic stem cells
Alpha satellite RNA marks the perinucleolar compartment and represses ribosomal RNA expression in naïve human embryonic stem cells

Authors: Mittal K, Ataei L, Ramalho-Santos M.

Reference: bioRxiv, 2025.07.11.664446; doi: 10.1101/2025.07.11.664446

20 years of stemness: From stem cells to hypertranscription and back
20 years of stemness: From stem cells to hypertranscription and back

Authors: Kim YK, Ramalho-Santos M.
Reference: Stem Cell Reports, 2025 Mar 11;20(3):102406. doi: /10.1016/j.stemcr.2025.102406
PMID: 39919752

2024

Featured
LINE1 elements at distal junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells
LINE1 elements at distal junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells

Authors: Ataei L, Zhang J, Monis S, Giemza K, Mittal K, Yang J, Shimomura M, McStay B, Wilson MD, Ramalho-Santos M.
Reference: Genes Dev, 2025 Feb 3;39(3-4):280-298. doi: 10.1101/gad.351979.124
PMID: 39797762

LINE1 and PRC2 control nucleolar organization and repression of the 8C state in human ESCs
LINE1 and PRC2 control nucleolar organization and repression of the 8C state in human ESCs

Authors: Zhang J, Ataei L, Mittal K, Wu L, Caldwell L, Huynh L, Sarajideen S, Tse K, Simon MM, Mazid A, Cook DP, Trcka D, Kwan T, Hoffman MM, Wrana JL, Esteban MA, Ramalho-Santos M.

Reference: Developmental Cell, 2024. https://doi.org/10.1016/j.devcel.2024.09.024

Hypertranscription: the invisible hand in stem cell biology
Hypertranscription: the invisible hand in stem cell biology

Authors: Kim YK, Collignon E, Martin SB, Ramalho-Santos M.

Reference: Trends in Genetics, 2024, https://doi.org/10.1016/j.tig.2024.08.005

2023

Featured
Evelyn_Sep_2023_figure.png
m6A RNA methylation orchestrates transcriptional dormancy during paused pluripotency

Authors: Collignon E, Cho B, Furlan G, Fothergill-Robinson J, Martin SB, McClymont SA, Ross RL, Limbach PA, Ramalho-Santos M.

Reference: Nature Cell Biology, 2023, https://doi.org/10.1038/s41556-023-01212-x

Kim et al 12072022 Graphical Abstract.tif.jpg
Absolute scaling of single-cell transcriptomes identifies pervasive hypertranscription in adult stem and progenitor cells

Authors: Kim YK, Cho B, Cook DP, Trcka D, Wrana JL, Ramalho-Santos M.

Reference: Cell Reports, 2023, https://www.cell.com/cell-reports/fulltext/S2211-1247(22)01882-4

2022

Featured
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Regulation, functions and transmission of bivalent chromatin during mammalian development

Authors: Macrae TA, Fothergill-Robinson J, Ramalho-Santos M.

Reference: Nat Rev Mol Cell Bio, https://doi.org/10.1038/s41580-022-00518-2

2021

Featured
1-s2.0-S2666166721004330-fx1_lrg.jpg
Depletion of nuclear LINE1 RNA in mouse ESCs and embryos

Authors: Percharde M, Lin CJ, Ramalho-Santos M.

Reference: STAR Protoc, 2021 Aug 9;2(3):100726. doi: 10.1016/j.xpro.2021.100726

PMID: 34409306

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Chd1 regulates repair of promoter-proximal DNA breaks to sustain hypertranscription in embryonic stem cells

Authors: Bulut-Karslioglu A, Jin H, Kim YK, Cho B, Guzman-Ayala M, JK Williamson A, Hejna M, Stötzel M, Whetton AD, S. Song J, Ramalho-Santos M

Reference: Nature Communications, 2021 Aug 11;12(1):4859.

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The deubiquitinase Usp9x regulates PRC2-mediated chromatin reprogramming during mouse development

Authors: Macrae TA, Ramalho-Santos M.

Reference: Nature Communications. 2021 Mar 25;12(1):1865.

PMID: 33767158

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Homotypic clustering of L1 and B1/Alu repeats compartmentalizes the 3D genome

Authors: Lu JY, Chang L, Li T, Wang T, Yin Y, Zhan G, Han X, Zhang K, Tao Y, Percharde M, Wang L, Peng Q, Yan P, Zhang H, Bi X, Shao W, Hong Y, Wu Z, Ma R, Wang P, Li W, Zhang J, Chang Z, Hou Y, Zhu B, Santos MR, Li P, Xie W, Na J, Sun Y, Shen X.

Reference : Cell Research. 2021 Jan 29, 10.1038/s41422-020-00466-6

PMID: 33514913

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Colorectal Cancer Cells Enter a Diapause-like DTP State to Survive Chemotherapy

Authors: Rehman AK, Haynes J, Collignon E, Brown KR, Wang Y, Nixon AML, Bruce JP, Wintersinger JA, Mer AS, Lo EBL, Leung C, Lima-Fernandes E, Pedley NM, Soares F, McGibbon S, He HH, Pollet A, Pugh TJ, Haibe-Kains B, Morris Q, Ramalho-Santos M, Goyal S, Moffat J, O'Brien CA

Reference :Cell. 2021 Jan 7; 184(1):226-242.

PMID: 33417860

2020

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Sex-specific epigenetic profile of inner cell mass of mice conceived in vivo or by IVF

Authors: Ruggeri E, Lira-Albarrán S, Grow EJ, Liu X, Harner R, Maltepe E, Ramalho-Santos M, Donjacour A, Rinaudo P.
Reference: Mol Hum Reprod. 2020 Nov 1;26(11):866-878. doi: 10.1093/molehr/gaaa064.
PMID: 33010164

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Genomic Repeats Categorize Genes with Distinct Functions for Orchestrated Regulation

Authors: Lu JY, Shao W, Chang L, Yin Y, Li T, Zhang H, Hong Y, Percharde M, Guo L, Wu Z, Liu L, Liu W, Yan P, Ramalho-Santos M, Sun Y, Shen X.

Reference: Cell Rep. 2020 Mar 10; 30 (10) :3296-3311
PMID: 32160538

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What Doesn’t Kill You Makes You Stronger: Transposons as Dual Players in Chromatin Regulation and Genomic Variation

Authors: Percharde M, Sultana T, Ramalho-Santos M.
Reference: Bioessays. 2020 Feb 13. https://onlinelibrary.wiley.com/doi/full/10.1002/bies.201900232
PMID: 32053231

 

2019

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Maternal vitamin C regulates reprogramming of DNA methylation and germline development

Authors: DiTroia SP, Percharde M, Guerquin MJ, Wall E, Collignon E, Ebata KT, Mesh K, Mahesula S, Agathocleous M, Laird DJ, Livera G, Ramalho-Santos M.
Reference: Nature. 2019 Sep 04. https://doi.org/10.1038/s41586-019-1536-1
PMID: 31719689

2018

Featured
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A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity.

Authors: Percharde M, Lin CJ, Yin Y, Guan J, Peixoto GA, Bulut-Karslioglu A, Biechele S, Huang B, Shen X, Ramalho-Santos M.
Reference: Cell. 2018 Jun 19. pii: S0092-8674(18)30655-X. doi: 10.1016/j.cell.2018.05.043.
PMID: 29937225

The Transcriptionally Permissive Chromatin State of Embryonic Stem Cells Is Acutely Tuned to Translational Output.
The Transcriptionally Permissive Chromatin State of Embryonic Stem Cells Is Acutely Tuned to Translational Output.

Authors: Bulut-Karslioglu A, Macrae TA, Oses-Prieto JA, Covarrubias S, Percharde M, Ku G, Diaz A, McManus MT, Burlingame AL, Ramalho-Santos M.
Reference: Cell Stem Cell. 2018 Mar 1;22(3):369-383.e8. doi: 10.1016/j.stem.2018.02.004.
PMID: 29499153

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Tet2 Rescues Age-Related Regenerative Decline and Enhances Cognitive Function in the Adult Mouse Brain.

Authors: Gontier G, Iyer M, Shea JM, Bieri G, Wheatley EG, Ramalho-Santos M, Villeda SA.
Reference: Cell Rep. 2018 Feb 20;22(8):1974-1981. doi: 10.1016/j.celrep.2018.02.001.
PMID: 29466726

2017

Featured
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Vitamin C induces specific demethylation of H3K9me2 in mouse embryonic stem cells via Kdm3a/b.

Authors: Ebata KT, Mesh K, Liu S, Bilenky M, Fekete A, Acker MG, Hirst M, Garcia BA, Ramalho-Santos M.
Reference: Epigenetics Chromatin. 2017 Jul 12;10:36. doi: 10.1186/s13072-017-0143-3. eCollection 2017.
PMID: 28706564

CHD1 loss sensitizes prostate cancer to DNA damaging therapy by promoting error-prone double-strand break repair

Authors: Shenoy TR, Boysen G, Wang MY, Xu QZ, Guo W, Koh FM, Wang C, Zhang LZ, Wang Y, Gil V, Aziz S, Christova R, Rodrigues DN, Crespo M, Rescigno P, Tunariu N, Riisnaes R, Zafeiriou Z, Flohr P, Yuan W, Knight E, Swain A, Ramalho-Santos M, Xu DY, de Bono J, Wu H.
Reference: Ann Oncol. 2017 Jul 1;28(7):1495-1507. doi: 10.1093/annonc/mdx165.
PMID: 28383660

Global Hypertranscription in the Mouse Embryonic Germline

Authors: Percharde M, Wong P, Ramalho-Santos M.
Reference: Cell Rep. 2017 Jun 6;19(10):1987-1996. doi: 10.1016/j.celrep.2017.05.036.
PMID: 28591571

Hypertranscription in Development, Stem Cells, and Regeneration.

Authors: Percharde M, Bulut-Karslioglu A, Ramalho-Santos M.
Reference: Dev Cell. 2017 Jan 9;40(1):9-21. doi: 10.1016/j.devcel.2016.11.010. Epub 2016 Dec 15. Review.
PMID: 27989554

2016

Featured
Inhibition of mTOR induces a paused pluripotent state.

Authors: Bulut-Karslioglu A, Biechele S, Jin H, Macrae TA, Hejna M, Gertsenstein M, Song JS, Ramalho-Santos M.
Reference: Nature. 2016 Dec 1;540(7631):119-123. doi: 10.1038/nature20578. Epub 2016 Nov 23.
PMID: 27880763

YAP Induces Human Naive Pluripotency.

Authors: Qin H, Hejna M, Liu Y, Percharde M, Wossidlo M, Blouin L, Durruthy-Durruthy J, Wong P, Qi Z, Yu J, Qi LS, Sebastiano V, Song JS, Ramalho-Santos M.
Reference: Cell Rep. 2016 Mar 15;14(10):2301-12. doi: 10.1016/j.celrep.2016.02.036. Epub 2016 Mar 3.
PMID: 26947063

2015

Featured
Unwind and transcribe: chromatin reprogramming in the early mammalian embryo.

Authors: Biechele S, Lin CJ, Rinaudo PF, Ramalho-Santos M.
Reference: Curr Opin Genet Dev. 2015 Oct;34:17-23. doi: 10.1016/j.gde.2015.06.003. Epub 2015 Jul 13. Review.
PMID: 26183187 

Emergence of hematopoietic stem and progenitor cells involves a Chd1-dependent increase in total nascent transcription.

Authors: Koh FM, Lizama CO, Wong P, Hawkins JS, Zovein AC, Ramalho-Santos M.
Reference: Proc Natl Acad Sci U S A. 2015 Apr 7;112(14):E1734-43. doi: 10.1073/pnas.1424850112. Epub 2015 Mar 23.
PMID: 25831528

HiTSelect: a comprehensive tool for high-complexity-pooled screen analysis.

Authors: Diaz AA, Qin H, Ramalho-Santos M, Song JS.
Reference: Nucleic Acids Res. 2015 Feb 18;43(3):e16. doi: 10.1093/nar/gku1197. Epub 2014 Nov 26.
PMID: 25428347

Chd1 is essential for the high transcriptional output and rapid growth of the mouse epiblast.

Authors: Guzman-Ayala M, Sachs M, Koh FM, Onodera C, Bulut-Karslioglu A, Lin CJ, Wong P, Nitta R, Song JS, Ramalho-Santos M.
Reference: Development. 2015 Jan 1;142(1):118-27. doi: 10.1242/dev.114843. Epub 2014 Dec 5.
PMID: 25480920

2014

Featured
A comparative encyclopedia of DNA elements in the mouse genome.

‍ ‍

Authors: Yue F, Cheng Y, Breschi A, et al.
Reference: Nature. 2014 Nov 20;515(7527):355-64. doi: 10.1038/nature13992.
PMID: 25409824

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Hira-mediated H3.3 incorporation is required for DNA replication and ribosomal RNA transcription in the mouse zygote.

Authors: Lin CJ, Koh FM, Wong P, Conti M, Ramalho-Santos M.
Reference: Dev Cell. 2014 Aug 11;30(3):268-79. doi: 10.1016/j.devcel.2014.06.022. Epub 2014 Jul 31.
PMID: 25087892

Systematic identification of barriers to human iPSC generation.

Authors: Qin H, Diaz A, Blouin L, Lebbink RJ, Patena W, Tanbun P, LeProust EM, McManus MT, Song JS, Ramalho-Santos M.
Reference: Cell. 2014 Jul 17;158(2):449-461. doi: 10.1016/j.cell.2014.05.040.
PMID: 25036638

2013

Featured
Somatic cells regulate maternal mRNA translation and developmental competence of mouse oocytes.

Authors: Chen J, Torcia S, Xie F, Lin CJ, Cakmak H, Franciosi F, Horner K, Onodera C, Song JS, Cedars MI, Ramalho-Santos M, Conti M.
Reference: Nat Cell Biol. 2013 Dec;15(12):1415-23. doi: 10.1038/ncb2873. Epub 2013 Nov 24.
PMID: 24270888 

Histone variant H3.3 maintains a decondensed chromatin state essential for mouse preimplantation development.

Authors: Lin CJ, Conti M, Ramalho-Santos M.
Reference: Development. 2013 Sep;140(17):3624-34. doi: 10.1242/dev.095513. Epub 2013 Jul 31.
PMID: 23903189

Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells.

Authors: Blaschke K, Ebata KT, Karimi MM, Zepeda-Martínez JA, Goyal P, Mahapatra S, Tam A, Laird DJ, Hirst M, Rao A, Lorincz MC, Ramalho-Santos M.
Reference: Nature. 2013 Aug 8;500(7461):222-6. doi: 10.1038/nature12362. Epub 2013 Jun 30.
PMID: 23812591

Bivalent chromatin marks developmental regulatory genes in the mouse embryonic germline in vivo.

Authors: Sachs M, Onodera C, Blaschke K, Ebata KT, Song JS, Ramalho-Santos M.
Reference: Cell Rep. 2013 Jun 27;3(6):1777-84. doi: 10.1016/j.celrep.2013.04.032. Epub 2013 May 30.
PMID: 23727241

Smad2 is essential for maintenance of the human and mouse primed pluripotent stem cell state.

Authors: Sakaki-Yumoto M, Liu J, Ramalho-Santos M, Yoshida N, Derynck R.
Reference: J Biol Chem. 2013 Jun 21;288(25):18546-60. doi: 10.1074/jbc.M112.446591. Epub 2013 May 6.
PMID: 23649632

2012

Featured
Transcriptional analysis of pluripotency reveals the Hippo pathway as a barrier to reprogramming.

Authors: Qin H, Blaschke K, Wei G, Ohi Y, Blouin L, Qi Z, Yu J, Yeh RF, Hebrok M, Ramalho-Santos M.
Reference: Hum Mol Genet. 2012 May 1;21(9):2054-67. doi: 10.1093/hmg/dds023. Epub 2012 Jan 27.
PMID: 22286172

Polycomb-like 3 promotes polycomb repressive complex 2 binding to CpG islands and embryonic stem cell self-renewal.

Authors: Hunkapiller J, Shen Y, Diaz A, Cagney G, McCleary D, Ramalho-Santos M, Krogan N, Ren B, Song JS, Reiter JF.
Reference: PLoS Genet. 2012;8(3):e1002576. doi: 10.1371/journal.pgen.1002576. Epub 2012 Mar 15.
PMID: 22438827

2011

Featured
Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells.

Authors: Ohi Y, Qin H, Hong C, Blouin L, Polo JM, Guo T, Qi Z, Downey SL, Manos PD, Rossi DJ, Yu J, Hebrok M, Hochedlinger K, Costello JF, Song JS, Ramalho-Santos M.
Reference: Nat Cell Biol. 2011 May;13(5):541-9. doi: 10.1038/ncb2239. Epub 2011 Apr 17.
PMID: 21499256

Open chromatin in pluripotency and reprogramming.

Authors: Gaspar-Maia A, Alajem A, Meshorer E, Ramalho-Santos M.
Reference: Nat Rev Mol Cell Biol. 2011 Jan;12(1):36-47. doi: 10.1038/nrm3036. Review. Erratum in: Nat Rev Mol Cell Biol. 2011 Apr;12(4):273.
PMID: 21179060

2010

Featured
Parallel gateways to pluripotency: open chromatin in stem cells and development.

Authors: Koh FM, Sachs M, Guzman-Ayala M, Ramalho-Santos M.
Reference: Curr Opin Genet Dev. 2010 Oct;20(5):492-9. doi: 10.1016/j.gde.2010.06.002. Epub 2010 Jul 2. Review.
PMID: 20598875

2009

Featured
iPS cells: insights into basic biology.

Authors: Ramalho-Santos M.
Reference: Cell. 2009 Aug 21;138(4):616-8. doi: 10.1016/j.cell.2009.08.012.
PMID: 19703387

Chd1 regulates open chromatin and pluripotency of embryonic stem cells.

Authors: Gaspar-Maia A, Alajem A, Polesso F, Sridharan R, Mason MJ, Heidersbach A, Ramalho-Santos J, McManus MT, Plath K, Meshorer E, Ramalho-Santos M.
Reference: Nature. 2009 Aug 13;460(7257):863-8. doi: 10.1038/nature08212. Epub 2009 Jul 8.
PMID: 19587682

2008

Featured
CompMoby: comparative MobyDick for detection of cis-regulatory motifs.

Authors: Chaivorapol C, Melton C, Wei G, Yeh RF, Ramalho-Santos M, Blelloch R, Li H.
Reference: BMC Bioinformatics. 2008 Oct 27;9:455. doi: 10.1186/1471-2105-9-455.
PMID: 18950538

The pluripotent transcriptome.

Authros: Grskovic M, Ramalho-Santos M.
Reference: StemBook [Internet]. Cambridge (MA): Harvard Stem Cell Institute; 2008-. 2008 Oct 10.
PMID: 20614622

High-efficiency stem cell fusion-mediated assay reveals Sall4 as an enhancer of reprogramming.

Authors: Wong CC, Gaspar-Maia A, Ramalho-Santos M, Reijo Pera RA.
Reference: PLoS One. 2008 Apr 16;3(4):e1955. doi: 10.1371/journal.pone.0001955.
PMID: 18414659

2007

Featured
Generation of induced pluripotent stem cells in the absence of drug selection.

Authors: Blelloch R, Venere M, Yen J, Ramalho-Santos M.
Reference: Cell Stem Cell. 2007 Sep 13;1(3):245-7. doi: 10.1016/j.stem.2007.08.008. Epub 2007 Sep 6. No abstract available.
PMID: 18371358

Systematic identification of cis-regulatory sequences active in mouse and human embryonic stem cells.

Authors: Grskovic M, Chaivorapol C, Gaspar-Maia A, Li H, Ramalho-Santos M.
Reference: PLoS Genet. 2007 Aug;3(8):e145.
PMID: 17784790

On the origin of the term "stem cell".

Authors: Ramalho-Santos M, Willenbring H.
Reference: Cell Stem Cell. 2007 Jun 7;1(1):35-8. doi: 10.1016/j.stem.2007.05.013.
PMID: 18371332

2006

Featured
RNA interference in embryonic stem cells and the prospects for future therapies.

Authors: Heidersbach A, Gaspar-Maia A, McManus MT, Ramalho-Santos M.
Reference: Gene Ther. 2006 Mar;13(6):478-86. Review.
PMID: 16520820

2004

Featured
Stem cells as probabilistic self-producing entities.

Authors: Ramalho-Santos M.
Reference: Bioessays. 2004 Sep;26(9):1013-6.
PMID: 15351971

2002

Featured
"Stemness": transcriptional profiling of embryonic and adult stem cells.

Authors: Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA.
Reference: Science. 2002 Oct 18;298(5593):597-600. Epub 2002 Sep 12.
PMID: 12228720

2001

Featured
Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R symmetry by the mouse node.

Authors: Zhang XM, Ramalho-Santos M, McMahon AP.
Reference: Cell. 2001 Jul 27;106(2):781-92.
PMID: 11517919

2000

Featured
Hedgehog signals regulate multiple aspects of gastrointestinal development.

Authors: Ramalho-Santos M, Melton DA, McMahon AP.
Reference: Development. 2000 Jun;127(12):2763-72.
PMID: 10821773

Will cell alliance breed bureaucracy and leave contributors out?

Authors: Haggarty SJ, Ramalho-Santos M.
Reference: Nature. 2000 Feb 10;403(6770):591. No abstract available.
PMID: 10688171

1999

Featured
Cloning and characterization of cDNA encoding cardosin A, an RGD-containing plant aspartic proteinase.

Authors: Faro C, Ramalho-Santos M, Vieira M, Mendes A, Simões I, Andrade R, Veríssimo P, Lin X, Tang J, Pires E.
Reference: J Biol Chem. 1999 Oct 1;274(40):28724-9.
PMID: 10497243

1998

Featured
Identification and proteolytic processing of procardosin A.

Authors: Ramalho-Santos M, Veríssimo P, Cortes L, Samyn B, Van Beeumen J, Pires E, Faro C.
Reference: Eur J Biochem. 1998 Jul 1;255(1):133-8.
PMID: 9692911

Cardosinogen A. The precursor form of the major aspartic proteinase from cardoon.

Authors: Ramalho-Santos M, Pissarra J, Pires E, Faro C.
Reference: Adv Exp Med Biol. 1998;436:253-8. No abstract available.
PMID: 9561227

A comparative study on the aspartic proteinases from different species of Cynara.

Authors: Veríssimo P, Ramalho-Santos M, Faro C, Pires E.
Referece: Adv Exp Med Biol. 1998;436:459-63. Review. No abstract available.
PMID: 9561253

Structural and functional aspects of cardosins.

Authors: Faro C, Ramalho-Santos M, Veríssimo P, Pissarra J, Frazão C, Costa J, Lin XL, Tang J, Pires E.
Reference: Adv Exp Med Biol. 1998;436:423-33. Review. No abstract available.
PMID: 9580379

1997

Featured
Cardosin A, an abundant aspartic proteinase, accumulates in protein storage vacuoles in the stigmatic papillae of Cynara cardunculus L.

Authors: Ramalho-Santos M, Pissarra J, Veríssimo P, Pereira S, Salema R, Pires E, Faro CJ.
Reference: Planta. 1997 Oct;203(2):204-12.
PMID: 9362566

1996

Featured
Action on bovine alpha s1-casein of cardosins A and B, aspartic proteinases from the flowers of the cardoon Cynara cardunculus L.

Authors: Ramalho-Santos M, Veríssimo P, Faro C, Pires E.
Reference: Biochim Biophys Acta. 1996 Sep 13;1297(1):83-9.
PMID: 8841384