Temporal perturbation of histone deacetylase activity reveals a requirement for HDAC1-3 in mesendoderm cell differentiation.

Autor:	Sinniah E; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia., Wu Z; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia., Shen S; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia., Naval-Sanchez M; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia., Chen X; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia., Lim J; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia; ARC Centre of Excellence for Advanced Molecular Imaging, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia., Helfer A; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia., Iyer A; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia; ARC Centre of Excellence for Advanced Molecular Imaging, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia., Tng J; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia; ARC Centre of Excellence for Advanced Molecular Imaging, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia., Lucke AJ; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia; ARC Centre of Excellence for Advanced Molecular Imaging, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia., Reid RC; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia; ARC Centre of Excellence for Advanced Molecular Imaging, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia., Redd MA; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia., Nefzger CM; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia., Fairlie DP; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia; ARC Centre of Excellence for Advanced Molecular Imaging, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia., Palpant NJ; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia. Electronic address: n.palpant@uq.edu.au.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 May 17; Vol. 39 (7), pp. 110818.
DOI:	10.1016/j.celrep.2022.110818
Abstrakt:	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.)
Databáze:	MEDLINE
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