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Publication : Lesion environments direct transplanted neural progenitors towards a wound repair astroglial phenotype in mice.

First Author  O'Shea TM Year  2022
Journal  Nat Commun Volume  13
Issue  1 Pages  5702
PubMed ID  36171203 Mgi Jnum  J:332341
Mgi Id  MGI:7343090 Doi  10.1038/s41467-022-33382-x
Citation  O'Shea TM, et al. (2022) Lesion environments direct transplanted neural progenitors towards a wound repair astroglial phenotype in mice. Nat Commun 13(1):5702
abstractText  Neural progenitor cells (NPC) represent potential cell transplantation therapies for CNS injuries. To understand how lesion environments influence transplanted NPC fate in vivo, we derived NPC expressing a ribosomal protein-hemagglutinin tag (RiboTag) for transcriptional profiling of transplanted NPC. Here, we show that NPC grafted into uninjured mouse CNS generate cells that are transcriptionally similar to healthy astrocytes and oligodendrocyte lineages. In striking contrast, NPC transplanted into subacute CNS lesions after stroke or spinal cord injury in mice generate cells that share transcriptional, morphological and functional features with newly proliferated host astroglia that restrict inflammation and fibrosis and isolate lesions from adjacent viable neural tissue. Our findings reveal overlapping differentiation potentials of grafted NPC and proliferating host astrocytes; and show that in the absence of other interventions, non-cell autonomous cues in subacute CNS lesions direct the differentiation of grafted NPC towards a naturally occurring wound repair astroglial phenotype.
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