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Direct pericyte-to-neuron reprogramming via unfolding of a neural stem cell-like program.
Nat. Neurosci. 21, 932–940 (2018)
Ectopic expression of defined transcription factors can force direct cell-fate conversion from one lineage to another in the absence of cell division. Several transcription factor cocktails have enabled successful reprogramming of various somatic cell types into induced neurons (iNs) of distinct neurotransmitter phenotype. However, the nature of the intermediate states that drive the reprogramming trajectory toward distinct iN types is largely unknown. Here we show that successful direct reprogramming of adult human brain pericytes into functional iNs by Ascl1 and Sox2 encompasses transient activation of a neural stem cell-like gene expression program that precedes bifurcation into distinct neuronal lineages. During this transient state, key signaling components relevant for neural induction and neural stem cell maintenance are regulated by and functionally contribute to iN reprogramming and maturation. Thus, Ascl1- and Sox2-mediated reprogramming into a broad spectrum of iN types involves the unfolding of a developmental program via neural stem cell-like intermediates.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Rna-seq; Direct Conversion; Gene-expression; Differentiation; Fibroblasts; Reveals; Activin; Neurogenesis; Interneurons; Mechanisms
ISSN (print) / ISBN
1097-6256
e-ISSN
1546-1726
Journal
Nature Neuroscience
Quellenangaben
Volume: 21,
Issue: 7,
Pages: 932–940
Publisher
Nature Publishing Group
Publishing Place
75 Varick St, 9th Flr, New York, Ny 10013-1917 Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Stem Cell Research (ISF)