Abstract
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.
Keywords:
DLX2; astrocytes; induced neural progenitor cells; in vivo reprogramming; scRNA-seq.
MeSH terms
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Animals
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Astrocytes / cytology*
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Astrocytes / metabolism*
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Cell Differentiation* / genetics
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Cell Lineage* / genetics
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Cellular Reprogramming* / genetics
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Corpus Striatum / cytology*
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Corpus Striatum / metabolism
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Fluorescent Antibody Technique
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GABAergic Neurons / cytology
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GABAergic Neurons / metabolism
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Gene Expression
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Gene Expression Profiling
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Gene Expression Regulation, Developmental
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Gene Regulatory Networks
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Genes, Reporter
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Mice
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Multipotent Stem Cells / cytology
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Multipotent Stem Cells / metabolism
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Neural Stem Cells / cytology
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Neural Stem Cells / metabolism
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Neurogenesis
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RNA-Seq
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Receptors, Notch / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Signal Transduction
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
Substances
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Ascl1 protein, mouse
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Basic Helix-Loop-Helix Transcription Factors
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Bcl11b protein, mouse
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Distal-less homeobox proteins
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Homeodomain Proteins
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Receptors, Notch
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Repressor Proteins
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Transcription Factors
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Tumor Suppressor Proteins