Human pluripotent stem cell culture density modulates YAP signaling

Cheston Hsiao, Michael Lampe, Songkhun Nillasithanukroh, Wenqing Han, Xiaojun Lian, Sean P. Palecek

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Human pluripotent stem cell (hPSC) density is an important factor in self-renewal and differentiation fates; however, the mechanisms through which hPSCs sense cell density and process this information in making cell fate decisions remain to be fully understood. One particular pathway that may prove important in density-dependent signaling in hPSCs is the Hippo pathway, which is regulated by cell-cell contact and mechanosensing through the cytoskeleton and has been linked to the maintenance of stem cell pluripotency. To probe regulation of Hippo pathway activity in hPSCs, we assessed whether Hippo pathway transcriptional activator YAP was differentially modulated by cell density. At higher cell densities, YAP phosphorylation and localization to the cytoplasm increased, which led to decreased YAP-mediated transcriptional activity. Furthermore, total YAP protein levels diminished at high cell density due to the phosphorylation-targeted degradation of YAP. Inducible shRNA knockdown of YAP reduced expression of YAP target genes and pluripotency genes. Finally, the density-dependent increase of neuroepithelial cell differentiation was mitigated by shRNA knockdown of YAP. Our results suggest a pivotal role of YAP in cell density-mediated fate decisions in hPSCs.

Original languageEnglish (US)
Pages (from-to)662-675
Number of pages14
JournalBiotechnology Journal
Volume11
Issue number5
DOIs
StatePublished - May 1 2016

All Science Journal Classification (ASJC) codes

  • Applied Microbiology and Biotechnology
  • Molecular Medicine

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    Hsiao, C., Lampe, M., Nillasithanukroh, S., Han, W., Lian, X., & Palecek, S. P. (2016). Human pluripotent stem cell culture density modulates YAP signaling. Biotechnology Journal, 11(5), 662-675. https://doi.org/10.1002/biot.201500374