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YAP1 regulates the self-organized fate patterning of hESC-derived gastruloids

Stronati, Eleonora
; 
Giraldez, Servando
; 
Huang, Ling
; ; ; 
Hsu, Hui-Ting
; 
Jones, Kathy A.
; 
Estarás, Conchi
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Journal article
Date
2022-01-20
Advisor
Committee member
Group
Center for Translational Medicine (Temple University)
Department
Cardiovascular Sciences
Subject
Micropatterns
 Gastrulation
 Gastruloids
 YAP1
 Hippo
 Nodal
 Smad2/3
 Ectoderm
 hESCs
 iPSCs
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http://hdl.handle.net/20.500.12613/9305
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StronatiEtAl-JournalArticle-2022-01.pdf
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http://dx.doi.org/10.1016/j.stemcr.2021.12.012
Abstract
The gastrulation process relies on complex interactions between developmental signaling pathways that are not completely understood. Here, we interrogated the contribution of the Hippo signaling effector YAP1 to the formation of the three germ layers by analyzing human embryonic stem cell (hESC)-derived 2D-micropatterned gastruloids. YAP1 knockout gastruloids display a reduced ectoderm layer and enlarged mesoderm and endoderm layers compared with wild type. Furthermore, our epigenome and transcriptome analysis revealed that YAP1 attenuates Nodal signaling by directly repressing the chromatin accessibility and transcription of key genes in the Nodal pathway, including the NODAL and FOXH1 genes. Hence, in the absence of YAP1, hyperactive Nodal signaling retains SMAD2/3 in the nuclei, impeding ectoderm differentiation of hESCs. Thus, our work revealed that YAP1 is a master regulator of Nodal signaling, essential for instructing germ layer fate patterning in human gastruloids.
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Citation
Eleonora Stronati, Servando Giraldez, Ling Huang, Elizabeth Abraham, Gillian R. McGuire, Hui-Ting Hsu, Kathy A. Jones, Conchi Estarás, YAP1 regulates the self-organized fate patterning of hESC-derived gastruloids, Stem Cell Reports, Volume 17, Issue 2, 2022, Pages 211-220, ISSN 2213-6711, https://doi.org/10.1016/j.stemcr.2021.12.012.
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Cell Press
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Stem Cell Reports, Vol. 17, Iss. 2
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