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Lesion environments direct transplanted neural progenitors towards a wound repair astroglial phenotype

View ORCID ProfileT.M. O’Shea, Y. Ao, S. Wang, A.L. Wollenberg, J.H. Kim, R.A. Ramos Espinoza, A. Czechanski, L.G Reinholdt, T.J. Deming, M.V. Sofroniew
doi: https://doi.org/10.1101/2022.01.24.477530
T.M. O’Shea
1Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1763, USA
2Department of Biomedical Engineering, Boston University, Boston, MA, 02215-2407, USA
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  • ORCID record for T.M. O’Shea
  • For correspondence: toshea@bu.edu sofroniew@mednet.ucla.edu
Y. Ao
1Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1763, USA
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S. Wang
1Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1763, USA
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A.L. Wollenberg
3Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, 90095-1600, USA
4Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095-1600, USA
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J.H. Kim
1Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1763, USA
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R.A. Ramos Espinoza
2Department of Biomedical Engineering, Boston University, Boston, MA, 02215-2407, USA
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A. Czechanski
5The Jackson Laboratory, Bar Harbor, ME 04609, USA
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L.G Reinholdt
5The Jackson Laboratory, Bar Harbor, ME 04609, USA
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T.J. Deming
3Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, 90095-1600, USA
4Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095-1600, USA
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M.V. Sofroniew
1Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1763, USA
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  • For correspondence: toshea@bu.edu sofroniew@mednet.ucla.edu mvs@g.ucla.edu
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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 CNS generate cells that are transcriptionally similar to healthy astrocytes and oligodendrocyte lineages. In striking contrast, NPC transplanted into serum-exposed CNS lesions after stroke or spinal cord injury generate cells that share transcriptional, morphological and functional features with newly proliferated host astroglia that restrict inflammation and fibrosis and thereby protect adjacent 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 CNS lesions direct the differentiation of grafted NPC predominantly towards a naturally occurring neuroprotective wound repair astroglial phenotype.

Competing Interest Statement

The authors have declared no competing interest.

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Posted January 25, 2022.
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Lesion environments direct transplanted neural progenitors towards a wound repair astroglial phenotype
T.M. O’Shea, Y. Ao, S. Wang, A.L. Wollenberg, J.H. Kim, R.A. Ramos Espinoza, A. Czechanski, L.G Reinholdt, T.J. Deming, M.V. Sofroniew
bioRxiv 2022.01.24.477530; doi: https://doi.org/10.1101/2022.01.24.477530
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Lesion environments direct transplanted neural progenitors towards a wound repair astroglial phenotype
T.M. O’Shea, Y. Ao, S. Wang, A.L. Wollenberg, J.H. Kim, R.A. Ramos Espinoza, A. Czechanski, L.G Reinholdt, T.J. Deming, M.V. Sofroniew
bioRxiv 2022.01.24.477530; doi: https://doi.org/10.1101/2022.01.24.477530

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