Heparan sulfate regulates the fate decisions of human pluripotent stem cells
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1-s2.0-S221367112400328X-main.pdf
Description
Published version
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5.42 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Syangtan, Deepsing
Al Mahbuba, Deena
Masuko, Sayaka
Li, Qiao
Elton, Andrew C
Zaltsman, Yefim
Wrighton, Paul J
Xia, Ke
Han, Xiaorui
Ouyang, Yilan
Date Issued
January 14, 2025
Journal
Stem Cell Reports
Publisher
Elsevier BV
Version
Final published version
Abstract
Heparan sulfate (HS) is an anionic polysaccharide generated by all animal cells, but our understanding of its roles in human pluripotent stem cell (hPSC) self-renewal and differentiation is limited. We derived HS-deficient hPSCs by disrupting the EXT1 glycosyltransferase. These EXT1−/− hPSCs maintain self-renewal and pluripotency under standard culture conditions that contain high levels of basic fibroblast growth factor(bFGF), a requirement for sufficient bFGF signaling in the engineered cells. Intriguingly, Activin/Nodal signaling is also compromised in EXT1−/− hPSCs, highlighting HS’s previously unexplored involvement in this pathway. As a result, EXT1−/− hPSCs fail to differentiate into mesoderm or endoderm lineages. Unexpectedly, HS is dispensable for early ectodermal differentiation of hPSCs but still critical in generating motor neurons. Those derived from HS-deficient hPSCs lack proper neuronal projections and show alterations in axonogenesis gene expression. Thus, our study uncovers expected and unexpected mechanistic roles of HS in hPSC fate decisions.
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Creative Commons Attribution-NonCommercial-NoDerivatives
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DOI of Published Version
https://doi.org/10.1016/j.stemcr.2024.11.014
