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Epigenetic and transcriptional regulations prime cell fate before division during human pluripotent stem cell differentiation

Author

Listed:
  • Pedro Madrigal

    (University of Cambridge
    Wellcome Genome Campus
    University of Cambridge
    European Bioinformatics Institute)

  • Siwei Deng

    (University of Oxford, Headington)

  • Yuliang Feng

    (University of Oxford, Headington)

  • Stefania Militi

    (University of Oxford, Headington)

  • Kim Jee Goh

    (University of Cambridge
    The Francis Crick Institute)

  • Reshma Nibhani

    (University of Oxford, Headington)

  • Rodrigo Grandy

    (University of Cambridge)

  • Anna Osnato

    (University of Cambridge)

  • Daniel Ortmann

    (University of Cambridge)

  • Stephanie Brown

    (University of Cambridge)

  • Siim Pauklin

    (University of Oxford, Headington)

Abstract

Stem cells undergo cellular division during their differentiation to produce daughter cells with a new cellular identity. However, the epigenetic events and molecular mechanisms occurring between consecutive cell divisions have been insufficiently studied due to technical limitations. Here, using the FUCCI reporter we developed a cell-cycle synchronised human pluripotent stem cell (hPSC) differentiation system for uncovering epigenome and transcriptome dynamics during the first two divisions leading to definitive endoderm. We observed that transcription of key differentiation markers occurs before cell division, while chromatin accessibility analyses revealed the early inhibition of alternative cell fates. We found that Activator protein-1 members controlled by p38/MAPK signalling are necessary for inducing endoderm while blocking cell fate shifting toward mesoderm, and that enhancers are rapidly established and decommissioned between different cell divisions. Our study has practical biomedical utility for producing hPSC-derived patient-specific cell types since p38/MAPK induction increased the differentiation efficiency of insulin-producing pancreatic beta-cells.

Suggested Citation

  • Pedro Madrigal & Siwei Deng & Yuliang Feng & Stefania Militi & Kim Jee Goh & Reshma Nibhani & Rodrigo Grandy & Anna Osnato & Daniel Ortmann & Stephanie Brown & Siim Pauklin, 2023. "Epigenetic and transcriptional regulations prime cell fate before division during human pluripotent stem cell differentiation," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36116-9
    DOI: 10.1038/s41467-023-36116-9
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    1. Jesse R. Dixon & Inkyung Jung & Siddarth Selvaraj & Yin Shen & Jessica E. Antosiewicz-Bourget & Ah Young Lee & Zhen Ye & Audrey Kim & Nisha Rajagopal & Wei Xie & Yarui Diao & Jing Liang & Huimin Zhao , 2015. "Chromatin architecture reorganization during stem cell differentiation," Nature, Nature, vol. 518(7539), pages 331-336, February.
    2. Rene C. Adam & Hanseul Yang & Shira Rockowitz & Samantha B. Larsen & Maria Nikolova & Daniel S. Oristian & Lisa Polak & Meelis Kadaja & Amma Asare & Deyou Zheng & Elaine Fuchs, 2015. "Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice," Nature, Nature, vol. 521(7552), pages 366-370, May.
    3. Michael J. Ziller & Reuven Edri & Yakey Yaffe & Julie Donaghey & Ramona Pop & William Mallard & Robbyn Issner & Casey A. Gifford & Alon Goren & Jeffrey Xing & Hongcang Gu & Davide Cacchiarelli & Alexa, 2015. "Dissecting neural differentiation regulatory networks through epigenetic footprinting," Nature, Nature, vol. 518(7539), pages 355-359, February.
    4. Alexander Favorov & Loris Mularoni & Leslie M Cope & Yulia Medvedeva & Andrey A Mironov & Vsevolod J Makeev & Sarah J Wheelan, 2012. "Exploring Massive, Genome Scale Datasets with the GenometriCorr Package," PLOS Computational Biology, Public Library of Science, vol. 8(5), pages 1-12, May.
    5. Timothy Bailey & Pawel Krajewski & Istvan Ladunga & Celine Lefebvre & Qunhua Li & Tao Liu & Pedro Madrigal & Cenny Taslim & Jie Zhang, 2013. "Practical Guidelines for the Comprehensive Analysis of ChIP-seq Data," PLOS Computational Biology, Public Library of Science, vol. 9(11), pages 1-8, November.
    6. Shane Neph & Jeff Vierstra & Andrew B. Stergachis & Alex P. Reynolds & Eric Haugen & Benjamin Vernot & Robert E. Thurman & Sam John & Richard Sandstrom & Audra K. Johnson & Matthew T. Maurano & Richar, 2012. "An expansive human regulatory lexicon encoded in transcription factor footprints," Nature, Nature, vol. 489(7414), pages 83-90, September.
    7. Alexander M. Tsankov & Hongcang Gu & Veronika Akopian & Michael J. Ziller & Julie Donaghey & Ido Amit & Andreas Gnirke & Alexander Meissner, 2015. "Transcription factor binding dynamics during human ES cell differentiation," Nature, Nature, vol. 518(7539), pages 344-349, February.
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