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Cited by 1Hippo pathway signaling and YAP/TAZDevelopmental Biology and Gene RegulationPluripotent Stem Cells Research

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YAP1 and QSER1 are key modulators of embryonic signaling pathways in the mammalian epiblast

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Abraham, Elizabeth, Roule, Thomas, Douglas, Aidan, Megill, Emily, Pericak, Olivia M, Howe, Jordan E, Choya-Foces, Carmen, Garbincius, Joanne F, Cohen, Henry M, Roig-Flórez, Paula, Zubillaga, Mikel, Andrake, Mark D, Kim, Seonhee, Elrod, John W, Akizu, Naiara, Estaras, Conchi·2026·EMBO Reports
DOI 10.1038/s44319-026-00746-zPMC PMC13172546

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Abstract

YAP1 signaling is essential for development but its specific roles in early embryogenesis remain poorly understood. To shed light on this, we analyze YAP1’s role in regulating the pluripotency of the mammalian epiblast, using scRNAseq approaches. Conditional deletion of Yap1 in the mouse epiblast ( Sox2 -Cre) alters the expression of signaling genes, including Nodal , Wnt3 , and Fgf8 . Accordingly, Yap1 loss leads to enhanced differentiation of the epiblast toward primitive streak lineages, as evidenced by the upregulation of T/ Brachyury and Eomes genes. A proximity labeling assay in human pluripotent stem cells, followed by biochemical assays and molecular modeling predictions, reveals that YAP1 cooperates with QSER1 protein to regulate lineage genes. Our analysis shows that YAP1:TEAD4 enhancers recruit QSER1 to prevent RNA Polymerase II recruitment. QSER1 depletion, similar to YAP1, increases NODAL gene expression and leads to hyperactive NODAL signaling during human embryonic stem cells differentiation. Overall, our findings define a role of YAP1 in the epiblast in vivo and uncover an interplay with QSER1 controlling the activity of developmental signaling pathways in pluripotent cells.

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Metadata

Authors
Abraham, E., Roule, T., Douglas, A., Megill, E., Pericak, O. M., Howe, J. E., Choya-Foces, C., Garbincius, J. F., Cohen, H. M., Roig-Flórez, P., Zubillaga, M., Andrake, M. D., Kim, S., Elrod, J. W., Akizu, N., & Estaras, C.
Affiliations
  • Temple University (US)
  • Fox Chase Cancer Center (US)
  • Children's Hospital of Philadelphia (US)
ORCID
Venue
EMBO Reports
Publisher
Springer Science and Business Media LLC
Published
2026-03-26
Volume
27
Issue
9
Pages
2369-2405
ISSN
  • 1469-221X (ISSN-L)
  • 1469-3178
DOI
10.1038/s44319-026-00746-z
PMC
PMC13172546
OpenAlex
W7140604682
Cited by
1
References
9
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • EMBO Reports (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • NIH/NICHD (HD106969, F31HD113419)
  • NIH/NHLBI (5T32HL091804)
  • NIH/NGMS (GM142606)
  • NIH/NINDS (R01NS119699)
  • NIH Cancer Center Support Grant P30 (CA006927)
  • NIH Cancer Center Support P30 (CA030199)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords
YAP, epiblast, pluripotency, Nodal signaling, Wnt3, FGF8, Brachyury, Eomes, RNA polymerase II recruitment, human pluripotent stem cells, early embryonic development

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