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These stem cells are specialized astrocytes, but astrocytes in other brain regions do not generate neurons under physiological conditions. After stroke, however, striatal astrocytes undergo neurogenesis in mice, triggered by decreased Notch signaling. We used single-cell RNA sequencing to characterize neurogenesis by Notch-depleted striatal astrocytes in vivo. Striatal astrocytes were located upstream of neural stem cells in the neuronal lineage. As astrocytes initiated neurogenesis, they became transcriptionally very similar to subventricular zone stem cells, progressing through a near-identical neurogenic program. Surprisingly, in the non-neurogenic cortex, Notch-depleted astrocytes also initiated neurogenesis. Yet, these cortical astrocytes, and many striatal ones, stalled before entering transit-amplifying divisions. Infusion of epidermal growth factor enabled stalled striatal astrocytes to resume neurogenesis. We conclude that parenchymal astrocytes are latent neural stem cells and that targeted interventions can guide them through their neuronal differentiation.<\/jats:p>","DOI":"10.7554\/elife.59733","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T08:01:47Z","timestamp":1596441707000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.59733","source":"Crossref","is-referenced-by-count":90,"title":["Activation of a neural stem cell transcriptional program in parenchymal astrocytes"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3928-8959","authenticated-orcid":true,"given":"Jens P","family":"Magnusson","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0664-4707","authenticated-orcid":true,"given":"Margherita","family":"Zamboni","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Santopolo","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff E","family":"Mold","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio","family":"Barrientos-Somarribas","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Talavera-Lopez","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5819-458X","authenticated-orcid":true,"given":"Jonas","family":"Fris\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2020,8,3]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1002\/cne.903570209","article-title":"Differential distribution of exogenous BDNF, NGF, and NT-3 in the brain corresponds to the relative abundance and distribution of high-affinity and low-affinity neurotrophin receptors","volume":"357","author":"Anderson","year":"1995","journal-title":"The Journal of Comparative Neurology"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/nargab\/lqaa017","article-title":"GSAn: an alternative to enrichment analysis for annotating gene sets","volume":"2","author":"Ayllon-Benitez","year":"2020","journal-title":"NAR Genomics and Bioinformatics"},{"key":"bib3","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.26945","article-title":"Mouse embryonic stem cells can differentiate via multiple paths to the same state","volume":"6","author":"Briggs","year":"2017","journal-title":"eLife"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"3581","DOI":"10.1073\/pnas.0709002105","article-title":"Origin and progeny of reactive gliosis: a source of multipotent cells in the injured brain","volume":"105","author":"Buffo","year":"2008","journal-title":"PNAS"},{"key":"bib5","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2006-7-10-r100","article-title":"CellProfiler: image analysis software for identifying and quantifying cell phenotypes","volume":"7","author":"Carpenter","year":"2006","journal-title":"Genome Biology"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/978-1-4939-9057-3_9","article-title":"Estimating differentiation potency of single cells using Single-Cell entropy (SCENT)","volume":"1935","author":"Chen","year":"2019","journal-title":"Comput. 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