@article{68ed19cc0e3043c28d988348debb778c,
title = "An Esrrb and Nanog Cell Fate Regulatory Module Controlled by Feed Forward Loop Interactions",
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 = "epigenetics, feed forward regulatory loops, multi-omics network, proteomics, stem cells",
author = "Ana Sevilla and Dimitri Papatsenko and Mazloom, {Amin R.} and Huilei Xu and Ana Vasileva and Unwin, {Richard D.} and Gary LeRoy and Chen, {Edward Y.} and Garrett-Bakelman, {Francine E.} and Lee, {Dung Fang} and Benjamin Trinite and Webb, {Ryan L.} and Zichen Wang and Jie Su and Julian Gingold and Ari Melnick and Garcia, {Benjamin A.} and Whetton, {Anthony D.} and MacArthur, {Ben D.} and Avi Ma{\textquoteright}ayan and Lemischka, {Ihor R.}",
note = "Funding Information: AW thanks the Leukaemia Lymphoma Research for funding. BG gratefully acknowledges funding support from an NIH Innovator award (DP2OD007447) from the Office of the Director, NIH, National Science Foundation (NSF) Early Faculty CAREER award and an NSF grant (CBET-0941143) and FG-B to the Sass Foundation Fellowship, NCI K08CA169055, and an American Society of Hematology (ASHAMFDP-20121) award under the ASH-AMFDP partnership with the Robert Wood Johnson Foundation. AS was funded by MINECO, the European Development Regional Fund (FEDER, PGC2018-098626-B100) and the Merck Salud Foundation. AS is a recipient of a Ram{\'o}n y Cajal contract (RYC-2016-19962). Funding Information: This research was funded by grants from the National Institutes of Health (NIH) to IL (5R01GM078465), the Empire State Stem Cell Fund through New York State Department of Health (NYSTEM) C024410 and C024176 (HESC-SRF) to IL: and NIH grants R01GM098316, P50GM071558, and R01DK088541-01A1 to AvM and D-FL is a New York Stem Cell Foundation Stanley and Fiona Druckenmiller Fellow. RU was funded, in part, by the Manchester Biomedical Research Centre. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Sevilla, Papatsenko, Mazloom, Xu, Vasileva, Unwin, LeRoy, Chen, Garrett-Bakelman, Lee, Trinite, Webb, Wang, Su, Gingold, Melnick, Garcia, Whetton, MacArthur, Ma{\textquoteright}ayan and Lemischka.",
year = "2021",
month = mar,
day = "19",
doi = "10.3389/fcell.2021.630067",
language = "English",
volume = "9",
journal = "Frontiers in Cell and Developmental Biology",
issn = "2296-634X",
publisher = "Frontiers Media S.A.",
}