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Sprouty genes regulate proliferation and survival of human embryonic stem cells

Hady Felfly1, Ophir D Klein

  • 1Program in Craniofacial and Mesenchymal Biology and Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, USA.

Scientific Reports
|July 25, 2013
PubMed

Insights

Sprouty (Spry) genes regulate human embryonic stem cell (hESC) self-renewal and survival. SPRY2 knockdown increased hESC death and impaired proliferation, while SPRY4 knockdown enhanced survival.

Area of Science:

  • Stem cell biology
  • Molecular signaling

Background:

  • Sprouty (Spry) genes are negative regulators of receptor tyrosine kinase (RTK) signaling.
  • RTK signaling is crucial for human embryonic stem cell (hESC) self-renewal and differentiation.
  • SPRY2 and SPRY4 are highly expressed in hESCs, suggesting a role in maintaining pluripotency.

Purpose of the Study:

  • To investigate the role of SPRY2 and SPRY4 in hESC self-renewal and survival.
  • To determine the effects of SPRY gene knockdown on hESC proliferation, differentiation, and cell death pathways.

Main Methods:

  • siRNA-mediated knockdown (KD) of SPRY2 and SPRY4 in hESCs.
  • Assessment of hESC proliferation, survival, and differentiation potential.
  • Analysis of cellular damage, including mitochondrial fusion and cell membrane integrity.

Main Results:

  • SPRY2 KD led to increased hESC cell death and reduced proliferation.
  • SPRY4 KD enhanced hESC survival.
  • Both SPRY2 and SPRY4 KD allowed differentiation into three germ layers, with a trend toward increased ectodermal differentiation after SPRY2 KD.
  • SPRY2 KD cells showed impaired mitochondrial fusion and cell membrane damage.

Conclusions:

  • Sprouty genes play critical roles in regulating proliferation and cell death in hESCs.
  • SPRY2 and SPRY4 have distinct, and sometimes opposing, roles in hESC maintenance.
  • Disruption of SPRY2 impacts cellular integrity, contributing to cell death.

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