title: Analysing human neural stem cell ontogeny by consecutive isolation of Notch active neural progenitors.
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.
authors: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Reuven
authors: R
authors: Edri
authors: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Yakey
authors: Y
authors: Yaffe
authors: 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors: Michael J
authors: MJ
authors: Ziller
authors: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Naresh
authors: N
authors: Mutukula
authors: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Rotem
authors: R
authors: Volkman
authors: Department of Cell Research and Immunology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Eyal
authors: E
authors: David
authors: 1] Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel [2] Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Jasmine
authors: J
authors: Jacob-Hirsch
authors: Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Hagar
authors: H
authors: Malcov
authors: Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Carmit
authors: C
authors: Levy
authors: 1] Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel [2] Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Gideon
authors: G
authors: Rechavi
authors: Department of Cell Research and Immunology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Irit
authors: I
authors: Gat-Viks
authors: 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors: Alexander
authors: A
authors: Meissner
authors: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Yechiel
authors: Y
authors: Elkabetz
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D002540:Cerebral Cortex / Q000196:embryology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D018613:Microscopy, Confocal; D054258:Neural Plate / Q000196:embryology; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D051880:Receptors, Notch