Analysing human neural stem cell ontogeny by consecutive isolation of Notch active neural progenitors

Reuven Edri, Yakey Yaffe, Michael J. Ziller, Naresh Mutukula, Rotem Volkman, Eyal David, Jasmine Jacob-Hirsch, Hagar Malcov, Carmit Levy, Gideon Rechavi, Irit Gat-Viks, Alexander Meissner and Yechiel Elkabetz ()
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Reuven Edri: Sackler School of Medicine, Tel Aviv University
Yakey Yaffe: Sackler School of Medicine, Tel Aviv University
Michael J. Ziller: Broad Institute of MIT and Harvard
Naresh Mutukula: Sackler School of Medicine, Tel Aviv University
Rotem Volkman: Sackler School of Medicine, Tel Aviv University
Eyal David: Faculty of Life Sciences, Tel Aviv University
Jasmine Jacob-Hirsch: Cancer Research Center, Chaim Sheba Medical Center
Hagar Malcov: Sackler School of Medicine, Tel Aviv University
Carmit Levy: Sackler School of Medicine, Tel Aviv University
Gideon Rechavi: Cancer Research Center, Chaim Sheba Medical Center
Irit Gat-Viks: Faculty of Life Sciences, Tel Aviv University
Alexander Meissner: Broad Institute of MIT and Harvard
Yechiel Elkabetz: Sackler School of Medicine, Tel Aviv University

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: Abstract Decoding heterogeneity of pluripotent stem cell (PSC)-derived neural progeny is fundamental for revealing the origin of diverse progenitors, for defining their lineages, and for identifying fate determinants driving transition through distinct potencies. Here we have prospectively isolated consecutively appearing PSC-derived primary progenitors based on their Notch activation state. We first isolate early neuroepithelial cells and show their broad Notch-dependent developmental and proliferative potential. Neuroepithelial cells further yield successive Notch-dependent functional primary progenitors, from early and midneurogenic radial glia and their derived basal progenitors, to gliogenic radial glia and adult-like neural progenitors, together recapitulating hallmarks of neural stem cell (NSC) ontogeny. Gene expression profiling reveals dynamic stage-specific transcriptional patterns that may link development of distinct progenitor identities through Notch activation. Our observations provide a platform for characterization and manipulation of distinct progenitor cell types amenable for developing streamlined neural lineage specification paradigms for modelling development in health and disease.

Date: 2015
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DOI: 10.1038/ncomms7500

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