Fate Specification of GFAP-Negative Primitive Neural Stem Cells and Their Progeny at Clonal Resolution.

Autor:	Yammine SZ; Department of Molecular Genetics, University of Toronto, Toronto, Canada., Burns I; Department of Molecular Genetics, University of Toronto, Toronto, Canada., Gosio J; Department of Molecular Genetics, University of Toronto, Toronto, Canada.; Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada., Peluso A; Department of Molecular Genetics, University of Toronto, Toronto, Canada., Merritt DM; Institute of Medical Science, University of Toronto, Toronto, Canada., Innes B; Department of Molecular Genetics, University of Toronto, Toronto, Canada., Coles BLK; Department of Molecular Genetics, University of Toronto, Toronto, Canada., Yan WR; Department of Molecular Genetics, University of Toronto, Toronto, Canada., Bader GD; Department of Molecular Genetics, University of Toronto, Toronto, Canada.; The Donnelly Centre and University of Toronto, Toronto, Canada., Morshead CM; The Donnelly Centre and University of Toronto, Toronto, Canada.; Department of Surgery, University of Toronto, Toronto, Canada., van der Kooy D; Department of Molecular Genetics, University of Toronto, Toronto, Canada.; The Donnelly Centre and University of Toronto, Toronto, Canada.
Jazyk:	angličtina
Zdroj:	Stem cells and development [Stem Cells Dev] 2023 Oct; Vol. 32 (19-20), pp. 606-621. Date of Electronic Publication: 2023 Sep 11.
DOI:	10.1089/scd.2023.0038
Abstrakt:	The mature brain contains an incredible number and diversity of cells that are produced and maintained by heterogeneous pools of neural stem cells (NSCs). Two distinct types of NSCs exist in the developing and adult mouse brain: Glial Fibrillary Acidic Protein (GFAP)-negative primitive (p)NSCs and downstream GFAP-positive definitive (d)NSCs. To better understand the embryonic functions of NSCs, we performed clonal lineage tracing within neurospheres grown from either pNSCs or dNSCs to enrich for their most immediate downstream neural progenitor cells (NPCs). These clonal progenitor lineage tracing data allowed us to construct a hierarchy of progenitor subtypes downstream of pNSCs and dNSCs that were then validated using single-cell transcriptomics. Further, we identify Nexn as required for neuronal specification from neuron/astrocyte progenitor cells downstream of rare pNSCs. Combined, these data provide single-cell resolution of NPC lineages downstream of rare pNSCs that likely would be missed from population-level analyses in vivo.
Databáze:	MEDLINE
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