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Type 3 inositol 1,4,5-trisphosphate receptor negatively regulates apoptosis during mouse embryonic stem cell

J Liang1, Y-J Wang, Y Tang

  • 1Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Cell Death and Differentiation
|January 16, 2010
PubMed

Insights

Type 3 inositol 1,4,5-trisphosphate receptors (IP(3)R3) regulate apoptosis and differentiation in embryonic stem (ES) cells. IP(3)R3 downregulation increases apoptosis and impairs mesodermal lineage commitment during early ES cell differentiation.

Area of Science:

  • Cellular Biology
  • Developmental Biology
  • Stem Cell Research

Background:

  • Inositol 1,4,5-trisphosphate receptors (IP(3)Rs) mediate crucial Ca(2+) signals involved in apoptosis and differentiation.
  • The specific roles of IP(3)Rs in pluripotent embryonic stem (ES) cell behavior are not well understood.

Purpose of the Study:

  • To investigate the function of type 3 IP(3)R (IP(3)R3) in regulating Ca(2+) signals, apoptosis, and differentiation in murine ES cells.
  • To elucidate the contribution of IP(3)R3 to early lineage commitment during ES cell differentiation.

Main Methods:

  • Utilized small interfering RNA (siRNA) for IP(3)R3 knockdown and overexpression in murine ES cells.
  • Analyzed Ca(2+) oscillations, apoptosis rates, and expression of lineage-specific markers (mesodermal, endodermal, ectodermal).
  • Assessed the impact of intracellular Ca(2+) chelation (BAPTA-AM) on apoptosis in IP(3)R3-manipulated cells.

Main Results:

  • IP(3)R3 expression was transiently downregulated during early ES cell differentiation, correlating with increased apoptosis.
  • IP(3)R3 knockdown enhanced apoptosis in differentiating cells and altered Ca(2+) oscillations, while overexpression had opposite effects.
  • IP(3)R3 knockdown suppressed the expression of mesodermal and mesoendodermal markers, impairing differentiation into these lineages, partly due to increased apoptosis in Flk-1(+) cells.

Conclusions:

  • IP(3)R3 plays a critical role in regulating apoptosis during early ES cell differentiation.
  • Modulation of Ca(2+) signals by IP(3)R3 is essential for proper lineage commitment in differentiating ES cells.
  • This study establishes IP(3)R3 as a key regulator of ES cell fate decisions through calcium signaling pathways.

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