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Stem Cell Reports. 2014 Dec 9;3(6):1015-28. doi: 10.1016/j.stemcr.2014.10.004. Epub 2014 Nov 13.

Endogenous WNT signaling regulates hPSC-derived neural progenitor cell heterogeneity and specifies their regional identity.

Author information

1
Department of Cellular and Molecular Medicine, Stem Cell Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0695, USA.
2
Department of Cellular and Molecular Medicine, Stem Cell Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0695, USA; School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85287-9709, USA.
3
UCSD and Scripps Institution of Oceanography, Scripps Genome Center, 9500 Gilman Drive, La Jolla, CA 92093-0202, USA.
4
Department of Cellular and Molecular Medicine, Stem Cell Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0695, USA. Electronic address: kwillert@ucsd.edu.
5
Department of Cellular and Molecular Medicine, Stem Cell Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0695, USA; School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85287-9709, USA. Electronic address: david.brafman@asu.edu.

Abstract

Neural progenitor cells (NPCs) derived from human pluripotent stem cells (hPSCs) are a multipotent cell population that is capable of nearly indefinite expansion and subsequent differentiation into the various neuronal and supporting cell types that comprise the CNS. However, current protocols for differentiating NPCs toward neuronal lineages result in a mixture of neurons from various regions of the CNS. In this study, we determined that endogenous WNT signaling is a primary contributor to the heterogeneity observed in NPC cultures and neuronal differentiation. Furthermore, exogenous manipulation of WNT signaling during neural differentiation, through either activation or inhibition, reduces this heterogeneity in NPC cultures, thereby promoting the formation of regionally homogeneous NPC and neuronal cultures. The ability to manipulate WNT signaling to generate regionally specific NPCs and neurons will be useful for studying human neural development and will greatly enhance the translational potential of hPSCs for neural-related therapies.

PMID:
25458891
PMCID:
PMC4264562
DOI:
10.1016/j.stemcr.2014.10.004
[Indexed for MEDLINE]
Free PMC Article

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