Frontiers in Cell and Developmental Biology (Mar 2021)
An Esrrb and Nanog Cell Fate Regulatory Module Controlled by Feed Forward Loop Interactions
- Ana Sevilla,
- Ana Sevilla,
- Ana Sevilla,
- Dimitri Papatsenko,
- Dimitri Papatsenko,
- Amin R. Mazloom,
- Huilei Xu,
- Ana Vasileva,
- Richard D. Unwin,
- Richard D. Unwin,
- Richard D. Unwin,
- Gary LeRoy,
- Edward Y. Chen,
- Francine E. Garrett-Bakelman,
- Dung-Fang Lee,
- Dung-Fang Lee,
- Benjamin Trinite,
- Ryan L. Webb,
- Zichen Wang,
- Jie Su,
- Jie Su,
- Julian Gingold,
- Julian Gingold,
- Ari Melnick,
- Benjamin A. Garcia,
- Anthony D. Whetton,
- Anthony D. Whetton,
- Ben D. MacArthur,
- Avi Ma’ayan,
- Ihor R. Lemischka,
- Ihor R. Lemischka,
- Ihor R. Lemischka
Affiliations
- Ana Sevilla
- Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Ana Sevilla
- Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Ana Sevilla
- Departament de Biología Cellular, Fisiología i Immunología, Facultat de Biología, Universitat de Barcelona, Barcelona, Spain
- Dimitri Papatsenko
- Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Dimitri Papatsenko
- Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Amin R. Mazloom
- Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Huilei Xu
- Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Ana Vasileva
- Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Richard D. Unwin
- Stem Cell and Leukaemia Proteomics Laboratory, School of Cancer and Enabling Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom
- Richard D. Unwin
- Academic Health Science Centre, Wolfson Molecular Imaging Centre, Manchester, United Kingdom
- Richard D. Unwin
- Centre for Advanced Discovery and Experimental Therapeutics, Central Manchester University Hospitals NHS Foundation Trust, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom
- Gary LeRoy
- Department of Molecular Biology, Princeton University, Princeton, NJ, United States
- Edward Y. Chen
- Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Francine E. Garrett-Bakelman
- Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, United States
- Dung-Fang Lee
- Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Dung-Fang Lee
- Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Benjamin Trinite
- 0Institut de Recerca de La Sida, IrsiCaixa AIDS Research Institute, Germans Trias I Pujol Research Institute, Hospital Universitari Germans Trias I Pujol, Catalonia, Spain
- Ryan L. Webb
- Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Zichen Wang
- Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Jie Su
- Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Jie Su
- Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Julian Gingold
- Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Julian Gingold
- Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Ari Melnick
- Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, United States
- Benjamin A. Garcia
- Department of Molecular Biology, Princeton University, Princeton, NJ, United States
- Anthony D. Whetton
- Stem Cell and Leukaemia Proteomics Laboratory, School of Cancer and Enabling Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom
- Anthony D. Whetton
- Academic Health Science Centre, Wolfson Molecular Imaging Centre, Manchester, United Kingdom
- Ben D. MacArthur
- 1The Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, United Kingdom
- Avi Ma’ayan
- Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Ihor R. Lemischka
- Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Ihor R. Lemischka
- Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Ihor R. Lemischka
- Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- DOI
- https://doi.org/10.3389/fcell.2021.630067
- Journal volume & issue
-
Vol. 9
Abstract
Cell fate decisions during development are governed by multi-factorial regulatory mechanisms including chromatin remodeling, DNA methylation, binding of transcription factors to specific loci, RNA transcription and protein synthesis. However, the mechanisms by which such regulatory “dimensions” coordinate cell fate decisions are currently poorly understood. Here we quantified the multi-dimensional molecular changes that occur in mouse embryonic stem cells (mESCs) upon depletion of Estrogen related receptor beta (Esrrb), a key pluripotency regulator. Comparative analyses of expression changes subsequent to depletion of Esrrb or Nanog, indicated that a system of interlocked feed-forward loops involving both factors, plays a central part in regulating the timing of mESC fate decisions. Taken together, our meta-analyses support a hierarchical model in which pluripotency is maintained by an Oct4-Sox2 regulatory module, while the timing of differentiation is regulated by a Nanog-Esrrb module.
Keywords
