1. Temporal perturbation of histone deacetylase activity reveals a requirement for HDAC1-3 in mesendoderm cell differentiation.
- Author
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Sinniah E, Wu Z, Shen S, Naval-Sanchez M, Chen X, Lim J, Helfer A, Iyer A, Tng J, Lucke AJ, Reid RC, Redd MA, Nefzger CM, Fairlie DP, and Palpant NJ
- Subjects
- Animals, Cell Differentiation genetics, Chromatin metabolism, Histone Deacetylase 1 genetics, Histone Deacetylase 1 metabolism, Histone Deacetylase 2 genetics, Histone Deacetylase 2 metabolism, Mice, Endoderm cytology, Endoderm enzymology, Endoderm metabolism, Histone Deacetylases genetics, Histone Deacetylases metabolism, Pluripotent Stem Cells cytology, Pluripotent Stem Cells enzymology, Pluripotent Stem Cells metabolism
- Abstract
Histone deacetylases (HDACs) are a class of enzymes that control chromatin state and influence cell fate. We evaluated the chromatin accessibility and transcriptome dynamics of zinc-containing HDACs during cell differentiation in vitro coupled with chemical perturbation to identify the role of HDACs in mesendoderm cell fate specification. Single-cell RNA sequencing analyses of HDAC expression during human pluripotent stem cell (hPSC) differentiation in vitro and mouse gastrulation in vivo reveal a unique association of HDAC1 and -3 with mesendoderm gene programs during exit from pluripotency. Functional perturbation with small molecules reveals that inhibition of HDAC1 and -3, but not HDAC2, induces mesoderm while impeding endoderm and early cardiac progenitor specification. These data identify unique biological functions of the structurally homologous enzymes HDAC1-3 in influencing hPSC differentiation from pluripotency toward mesendodermal and cardiac progenitor populations., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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