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Rho/ROCK pathway is essential to the expansion, differentiation, and morphological rearrangements of human neural stem/progenitor cells induced by lysophosphatidic acid

Journal Article


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Abstract


  • We previously reported that lysophosphatidic acid (LPA) inhibits the neuronal differentiation of human embryonic stem cells (hESC). We extended these studies by analyzing LPA's effects on the expansion of neural stem/ progenitor cells (NS/PC) derived from hESCs and human induced pluripotent stem cells (iPSC), and we assessed whether data obtained on the neural differentiation of hESCs were relevant to iPSCs. We showed that hESCs and iPSCs exhibited comparable mRNA expression profiles of LPA receptors and producing enzymes upon neural differentiation. We demonstrated that LPA inhibited the expansion of NS/PCs of both origins, mainly by increased apoptosis in a Rho/Rho-associated kinase (ROCK)-dependent mechanism. Furthermore, LPA inhibited the neuronal differentiation of iPSCs. Lastly, LPA induced neurite retraction of NS/ PC-derived early neurons through Rho/ROCK, which was accompanied by myosin light chain (MLC) phosphorylation. Our data demonstrate the consistency of LPA effects across various sources of human NS/PCs, rendering hESCs and iPSCs valuable models for studying lysophospholipid signaling in human neural cells. Our data also highlight the importance of the Rho/ROCK pathway in human NS/ PCs. As LPA levels are increased in the central nervous system (CNS) following injury, LPA-mediated effects on NS/ PCs and early neurons could contribute to the poor neurogenesis observed in the CNS following injury.

Authors


  •   Frisca, Frisca (external author)
  •   Crombie, Duncan E. (external author)
  •   Dottori, Mirella
  •   Goldshmit, Yona (external author)
  •   Pebay, Alice (external author)

Publication Date


  • 2013

Citation


  • Frisca, F., Crombie, D. E., Dottori, M., Goldshmit, Y. & Pebay, A. (2013). Rho/ROCK pathway is essential to the expansion, differentiation, and morphological rearrangements of human neural stem/progenitor cells induced by lysophosphatidic acid. Journal of Lipid Research, 54 (5), 1192-1206.

Scopus Eid


  • 2-s2.0-84876800996

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=2193&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1166

Has Global Citation Frequency


Number Of Pages


  • 14

Start Page


  • 1192

End Page


  • 1206

Volume


  • 54

Issue


  • 5

Place Of Publication


  • United States

Abstract


  • We previously reported that lysophosphatidic acid (LPA) inhibits the neuronal differentiation of human embryonic stem cells (hESC). We extended these studies by analyzing LPA's effects on the expansion of neural stem/ progenitor cells (NS/PC) derived from hESCs and human induced pluripotent stem cells (iPSC), and we assessed whether data obtained on the neural differentiation of hESCs were relevant to iPSCs. We showed that hESCs and iPSCs exhibited comparable mRNA expression profiles of LPA receptors and producing enzymes upon neural differentiation. We demonstrated that LPA inhibited the expansion of NS/PCs of both origins, mainly by increased apoptosis in a Rho/Rho-associated kinase (ROCK)-dependent mechanism. Furthermore, LPA inhibited the neuronal differentiation of iPSCs. Lastly, LPA induced neurite retraction of NS/ PC-derived early neurons through Rho/ROCK, which was accompanied by myosin light chain (MLC) phosphorylation. Our data demonstrate the consistency of LPA effects across various sources of human NS/PCs, rendering hESCs and iPSCs valuable models for studying lysophospholipid signaling in human neural cells. Our data also highlight the importance of the Rho/ROCK pathway in human NS/ PCs. As LPA levels are increased in the central nervous system (CNS) following injury, LPA-mediated effects on NS/ PCs and early neurons could contribute to the poor neurogenesis observed in the CNS following injury.

Authors


  •   Frisca, Frisca (external author)
  •   Crombie, Duncan E. (external author)
  •   Dottori, Mirella
  •   Goldshmit, Yona (external author)
  •   Pebay, Alice (external author)

Publication Date


  • 2013

Citation


  • Frisca, F., Crombie, D. E., Dottori, M., Goldshmit, Y. & Pebay, A. (2013). Rho/ROCK pathway is essential to the expansion, differentiation, and morphological rearrangements of human neural stem/progenitor cells induced by lysophosphatidic acid. Journal of Lipid Research, 54 (5), 1192-1206.

Scopus Eid


  • 2-s2.0-84876800996

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=2193&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1166

Has Global Citation Frequency


Number Of Pages


  • 14

Start Page


  • 1192

End Page


  • 1206

Volume


  • 54

Issue


  • 5

Place Of Publication


  • United States