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 |
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| Sprache: | Englisch |
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15.03.2022
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| ISSN: | 1091-6490, 1091-6490 |
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| 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. |
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| AbstractList | 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.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. 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. |
| Author | Zou, Yuhua Fu, Yang-Xin Zhang, Chun-Li Cananzi, Sergio Zhang, Yunjia Han, Chuanhui Li, Boxun Wang, Lei-Lei Hon, Gary C |
| Author_xml | – sequence: 1 givenname: Yunjia surname: Zhang fullname: Zhang, Yunjia organization: Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 – sequence: 2 givenname: Boxun orcidid: 0000-0002-4516-4418 surname: Li fullname: Li, Boxun organization: Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390 – sequence: 3 givenname: Sergio surname: Cananzi fullname: Cananzi, Sergio organization: Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 – sequence: 4 givenname: Chuanhui surname: Han fullname: Han, Chuanhui organization: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390 – sequence: 5 givenname: Lei-Lei surname: Wang fullname: Wang, Lei-Lei organization: Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 – sequence: 6 givenname: Yuhua surname: Zou fullname: Zou, Yuhua organization: Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 – sequence: 7 givenname: Yang-Xin orcidid: 0000-0001-8441-6617 surname: Fu fullname: Fu, Yang-Xin organization: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390 – sequence: 8 givenname: Gary C orcidid: 0000-0002-1615-0391 surname: Hon fullname: Hon, Gary C organization: Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390 – sequence: 9 givenname: Chun-Li surname: Zhang fullname: Zhang, Chun-Li organization: Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 |
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| Snippet | SignificanceOutside the neurogenic niches, the adult brain lacks multipotent progenitor cells. In this study, we performed a series of in vivo screens and... SignificanceOutside the neurogenic niches, the adult brain lacks multipotent progenitor cells. In this study, we performed a series of in vivo screens and... |
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| SubjectTerms | 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 |
| Title | A single factor elicits multilineage reprogramming of astrocytes in the adult mouse striatum |
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