Document Type

Article

Publication Date

9-28-2022

Publication Title

Nat Commun

Keywords

JMG, Animals, Astrocytes, Cell Differentiation, Hemagglutinins, Mice, Neural Stem Cells, Phenotype, Ribosomal Proteins, Spinal Cord Injuries, Stem Cell Transplantation

JAX Source

Nat Commun. 2022;13(1):5702

Volume

13

Issue

1

First Page

5702

Last Page

5702

ISSN

2041-1723

PMID

36171203

DOI

https://doi.org/10.1038/s41467-022-33382-x

Grant

Thanks to the UCLA Neuroscience Genomics Core for assistance with sequencing. This work was supported by US National Institutes of Health (NS084030 to M.V.S.); Dr. Miriam and Sheldon G. Adelson Medical Foundation (M.V.S. and T.J.D); Craig H. Neilsen Foundation (381357 to T.M.O.); Paralyzed Veterans Foundation of America (RF3170 to T.M.O.); American Australian Association (T.M.O.), Wings for Life Spinal Cord Research Foundation (M.V.S. and T.M.O.); US National Institutes of Health (OD010921 to L.G.R.); and Microscopy Core Resource of UCLA Broad Stem Cell Research Center.

Abstract

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.

Comments

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