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; Yechiel Elkabetz

doi:10.1038/ncomms7500

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, Yechiel Elkabetz

Research output: Contribution to journal › Article › peer-review

56 Scopus citations

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.

Original language	English
Article number	6500
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7500
State	Published - 23 Mar 2015
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.

Funding

We thank Lorenz Studer (Sloan-Kettering Institute, NY, USA) and his former lab members Mark Tomishima and Dimitris Placantonakis, for the invaluable HES5::eGFP hESC line. We thank Drora Halperin for her major contribution to culture techniques establishment, Diana Mashenko-Polotov for her fruitful comments and technical assistance, Daria Bloch, Justin Karlin, Stewart Barlow, Omer Ziv and other members of our group for their help in initiating this study, and I. Shur and Y. Berdichevsky for their extensive help in FACS operation. We also thank the French Friends of Tel-Aviv University and the David Birène and Lyne Gelrubin families, as well as the American Friends of Tel Aviv University and the Richard & Deb Sincere and Noni & Alan Aufzien families, for their great support of our research. This work was supported by the Israel Science Foundation (ISF1126/10, ISF1710/10) and the Marie Curie International Reintegration Grant (IRG277151).

Funders	Funder number
Seventh Framework Programme	277151
Israel Science Foundation	ISF1126/10, ISF1710/10, IRG277151

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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.",

author = "Reuven Edri and Yakey Yaffe and Ziller, {Michael J.} and Naresh Mutukula and Rotem Volkman and Eyal David and Jasmine Jacob-Hirsch and Hagar Malcov and Carmit Levy and Gideon Rechavi and Irit Gat-Viks and Alexander Meissner and Yechiel Elkabetz",

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AU - Volkman, Rotem

AU - David, Eyal

AU - Jacob-Hirsch, Jasmine

AU - Malcov, Hagar

AU - Levy, Carmit

AU - Rechavi, Gideon

AU - Gat-Viks, Irit

AU - Meissner, Alexander

AU - Elkabetz, Yechiel

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

Abstract

Bibliographical note

Funding

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