Histone H2AX-dependent GABA(A) receptor regulation of stem cell proliferation

Nature
Michael AndängPatrik Ernfors

Abstract

Stem cell self-renewal implies proliferation under continued maintenance of multipotency. Small changes in numbers of stem cells may lead to large differences in differentiated cell numbers, resulting in significant physiological consequences. Proliferation is typically regulated in the G1 phase, which is associated with differentiation and cell cycle arrest. However, embryonic stem (ES) cells may lack a G1 checkpoint. Regulation of proliferation in the 'DNA damage' S/G2 cell cycle checkpoint pathway is known for its role in the maintenance of chromatin structural integrity. Here we show that autocrine/paracrine gamma-aminobutyric acid (GABA) signalling by means of GABA(A) receptors negatively controls ES cell and peripheral neural crest stem (NCS) cell proliferation, preimplantation embryonic growth and proliferation in the boundary-cap stem cell niche, resulting in an attenuation of neuronal progenies from this stem cell niche. Activation of GABA(A) receptors leads to hyperpolarization, increased cell volume and accumulation of stem cells in S phase, thereby causing a rapid decrease in cell proliferation. GABA(A) receptors signal through S-phase checkpoint kinases of the phosphatidylinositol-3-OH kinase-related kinase family ...Continue Reading

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Citations

Nov 15, 2011·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·M SidorkiewiczJ Bartkowiak
May 5, 2012·Journal of Autism and Developmental Disorders·Jing-Qiong Kang, Gregory Barnes
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Jun 23, 2012·Nature·Giles RobinsonRichard J Gilbertson
Jun 10, 2008·Nature Protocols·Michael AndängPatrik Ernfors
May 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jiaxi ZhouFei Wang
Mar 26, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ruani N FernandoPatrik Ernfors
May 2, 2008·Stem Cells and Development·Annalena MolinerMichael Andäng
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