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

Author

Listed:
  • 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
    Harvard University)

  • 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
    Sackler School of Medicine, Tel Aviv University)

  • 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
    Sackler School of Medicine, Tel Aviv University)

  • Irit Gat-Viks

    (Faculty of Life Sciences, Tel Aviv University)

  • Alexander Meissner

    (Broad Institute of MIT and Harvard
    Harvard University)

  • Yechiel Elkabetz

    (Sackler School of Medicine, Tel Aviv University)

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.

Suggested Citation

  • 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 &, 2015. "Analysing human neural stem cell ontogeny by consecutive isolation of Notch active neural progenitors," Nature Communications, Nature, vol. 6(1), pages 1-15, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7500
    DOI: 10.1038/ncomms7500
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    Cited by:

    1. Balazs V. Varga & Maryam Faiz & Helena Pivonkova & Gabriel Khelifi & Huijuan Yang & Shangbang Gao & Emma Linderoth & Mei Zhen & Ragnhildur Thora Karadottir & Samer M. Hussein & Andras Nagy, 2022. "Signal requirement for cortical potential of transplantable human neuroepithelial stem cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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