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YAP Non-cell-autonomously Promotes Pluripotency Induction in Mouse Cells
Amaleah A Hartman1, S Maxwell Scalf1, Jian Zhang1
1Cell Biology Department, Yale University, 10 Amistad Street, Room 131H, New Haven, CT 06520, USA; Yale Stem Cell Center, Yale University, New Haven, CT 06520, USA.
Stem Cell Reports
|April 4, 2020
Summary
Yes-associated protein (YAP) has dual roles in stemness and pluripotency. This study reveals YAP inhibits pluripotency cell-autonomously but promotes it non-cell-autonomously via CYR61.
Area of Science:
- Cell Biology
- Developmental Biology
- Stem Cell Research
Background:
- Yes-associated protein (YAP) is a key regulator of cell proliferation, survival, and stemness.
- YAP exhibits context-dependent roles, promoting stemness but antagonizing pluripotency during early embryogenesis.
- The precise mechanisms underlying YAP's opposing functions in pluripotency remain elusive.
Purpose of the Study:
- To investigate the dual role of YAP in regulating pluripotency induction in mouse somatic cells.
- To elucidate the cell-autonomous and non-cell-autonomous mechanisms by which YAP influences pluripotency.
- To identify downstream factors mediating YAP's non-cell-autonomous effects on pluripotency.
Main Methods:
- Utilized mouse somatic cells for pluripotency induction experiments.
- Assessed YAP's effects on pluripotency both cell-autonomously and non-cell-autonomously.
- Analyzed changes in gene expression, particularly secreted and matricellular proteins, including CYR61.
- Employed recombinant CYR61 and CYR61 depletion strategies to validate findings.
Main Results:
- YAP demonstrated opposing effects on pluripotency induction depending on cellular context.
- YAP inhibited pluripotency induction in a cell-autonomous manner.
- YAP promoted pluripotency induction non-cell-autonomously, largely through the modulation of CYR61 expression.
- Recombinant CYR61 mimicked YAP's promoting effect, while CYR61 depletion abrogated it.
Conclusions:
- YAP-driven enhancement of pluripotency induction is significantly mediated by CYR61.
- Cell fate determination is influenced by interactions with neighboring cells, highlighting the importance of non-cell-autonomous signaling.
- Future studies should consider the impact of bystander cells in complex culture systems and tissues for a comprehensive understanding of cell fate control.
Keywords:
CYR61YAPYamanaka reprogrammingiPSCsnon-cell-autonomouspluripotencystem Cellyes-associated proteinMore Related Videos
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