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DNGR-1-tracing marks an ependymal cell subset with damage-responsive neural stem cell potential

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2022

Dev Cell. 2022 Aug 22;57(16):1957-1975.e9. doi: 10.1016/j.devcel.2022.07.012.

DNGR-1-tracing marks an ependymal cell subset with damage-responsive neural stem cell potential

Bruno Frederico, Isaura Martins, Diana Chapela, Francesca Gasparrini, Probir Chakravarty, Tobias Ackels, Cécile Piot, Bruna Almeida, Joana Carvalho, Alessandro Ciccarelli, Christopher J Peddie, Neil Rogers, James Briscoe, François Guillemot, Andreas T Schaefer, Leonor Saúde, Caetano Reis E Sousa

Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. TechnoPhage, SA, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal. Bioinformatics and Biostatistics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Sensory Circuits and Neurotechnology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Experimental Histopathology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Advanced Light Microscopy, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electron Microscopy, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Developmental Dynamic Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Neural Stem Cell Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Department of Neuroscience, Physiology &Pharmacology, University College London, London, UK. Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal; Instituto de Medicina Molecular e Instituto de Histologia e Biologia do Desenvolvimento, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal. Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.

Service type: Knock-in mice

Abstract

Cells with latent stem ability can contribute to mammalian tissue regeneration after damage. Whether the central nervous system (CNS) harbors such cells remains controversial. Here, we report that DNGR-1 lineage tracing in mice identifies an ependymal cell subset, wherein resides latent regenerative potential. We demonstrate that DNGR-1-lineage-traced ependymal cells arise early in embryogenesis (E11.5) and subsequently spread across the lining of cerebrospinal fluid (CSF)-filled compartments to form a contiguous sheet from the brain to the end of the spinal cord. In the steady state, these DNGR-1-traced cells are quiescent, committed to their ependymal cell fate, and do not contribute to neuronal or glial lineages. However, trans-differentiation can be induced in adult mice by CNS injury or in vitro by culture with suitable factors. Our findings highlight previously unappreciated ependymal cell heterogeneity and identify across the entire CNS an ependymal cell subset wherein resides damage-responsive neural stem cell potential.

Keywords: CLEC9A; dendritic cells; ependymal cells; neural stem cells; tissue repair.

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