A single factor elicits multilineage reprogramming of astrocytes in the adult mouse striatum

SignificanceOutside the neurogenic niches, the adult brain lacks multipotent progenitor cells. In this study, we performed a series of in vivo screens and reveal that a single factor can induce resident brain astrocytes to become induced neural progenitor cells (iNPCs), which then generate neurons,...

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Veröffentlicht in:	Proceedings of the National Academy of Sciences - PNAS Jg. 119; H. 11; S. e2107339119
Hauptverfasser:	Zhang, Yunjia, Li, Boxun, Cananzi, Sergio, Han, Chuanhui, Wang, Lei-Lei, Zou, Yuhua, Fu, Yang-Xin, Hon, Gary C, Zhang, Chun-Li
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 15.03.2022
Schlagworte:	Animals Astrocytes - cytology Astrocytes - metabolism Basic Helix-Loop-Helix Transcription Factors - genetics Cell Differentiation - genetics Cell Lineage - genetics Cellular Reprogramming - genetics Corpus Striatum - cytology Corpus Striatum - metabolism Fluorescent Antibody Technique GABAergic Neurons - cytology GABAergic Neurons - metabolism Gene Expression Gene Expression Profiling Gene Expression Regulation, Developmental Gene Regulatory Networks Genes, Reporter Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Mice Multipotent Stem Cells - cytology Multipotent Stem Cells - metabolism Neural Stem Cells - cytology Neural Stem Cells - metabolism Neurogenesis Receptors, Notch - metabolism Repressor Proteins - genetics Repressor Proteins - metabolism RNA-Seq Signal Transduction Transcription Factors - genetics Transcription Factors - metabolism Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism in vivo reprogramming induced neural progenitor cells DLX2 scRNA-seq astrocytes
ISSN:	1091-6490, 1091-6490
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Beschreibung
Zusammenfassung:	SignificanceOutside the neurogenic niches, the adult brain lacks multipotent progenitor cells. In this study, we performed a series of in vivo screens and reveal that a single factor can induce resident brain astrocytes to become induced neural progenitor cells (iNPCs), which then generate neurons, astrocytes, and oligodendrocytes. Such a conclusion is supported by single-cell RNA sequencing and multiple lineage-tracing experiments. Our discovery of iNPCs is fundamentally important for regenerative medicine since neural injuries or degeneration often lead to loss/dysfunction of all three neural lineages. Our findings also provide insights into cell plasticity in the adult mammalian brain, which has largely lost the regenerative capacity.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1091-6490 1091-6490
DOI:	10.1073/pnas.2107339119