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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Published in:Proceedings of the National Academy of Sciences - PNAS Vol. 119; no. 11; p. e2107339119
Main Authors: 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
Language:English
Published: United States 15.03.2022
Subjects:
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
Online Access:Get more information
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Summary: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.
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ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.2107339119