A branching model of lineage differentiation underpinning the neurogenic potential of enteric glia.

Autor: Laddach A; Nervous System Development and Homeostasis Laboratory, the Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK. Anna.Laddach@crick.ac.uk., Chng SH; Nervous System Development and Homeostasis Laboratory, the Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.; Experimental Drug Development Centre A*STAR 10 Biopolis Road, Chromos, 138670, Singapore., Lasrado R; Nervous System Development and Homeostasis Laboratory, the Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.; COMPASS Pathways PLC, Fora, 33 Broadwick St, London, W1F 0DQ, UK., Progatzky F; Nervous System Development and Homeostasis Laboratory, the Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK., Shapiro M; Nervous System Development and Homeostasis Laboratory, the Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK., Erickson A; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, 17165, Sweden., Sampedro Castaneda M; Kinases and Brain Development Laboratory, the Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK., Artemov AV; Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Bienna, 1090, Austria.; Boehringer Ingelheim RCV, Vienna, Austria., Bon-Frauches AC; Nervous System Development and Homeostasis Laboratory, the Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK., Amaniti EM; Nervous System Development and Homeostasis Laboratory, the Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.; Sainsbury Wellcome Centre, London, UK., Kleinjung J; Nervous System Development and Homeostasis Laboratory, the Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.; Sosei Heptares, Steinmetz Building, Granta Park, Great Abington, Cambridge, CB21 6DG, UK., Boeing S; Bioinformatics and Biostatistics Science Technology Platform, the Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK., Ultanir S; Kinases and Brain Development Laboratory, the Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK., Adameyko I; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, 17165, Sweden.; Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Bienna, 1090, Austria., Pachnis V; Nervous System Development and Homeostasis Laboratory, the Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK. Vassilis.Pachnis@crick.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Sep 22; Vol. 14 (1), pp. 5904. Date of Electronic Publication: 2023 Sep 22.
DOI: 10.1038/s41467-023-41492-3
Abstrakt: Glial cells have been proposed as a source of neural progenitors, but the mechanisms underpinning the neurogenic potential of adult glia are not known. Using single cell transcriptomic profiling, we show that enteric glial cells represent a cell state attained by autonomic neural crest cells as they transition along a linear differentiation trajectory that allows them to retain neurogenic potential while acquiring mature glial functions. Key neurogenic loci in early enteric nervous system progenitors remain in open chromatin configuration in mature enteric glia, thus facilitating neuronal differentiation under appropriate conditions. Molecular profiling and gene targeting of enteric glial cells in a cell culture model of enteric neurogenesis and a gut injury model demonstrate that neuronal differentiation of glia is driven by transcriptional programs employed in vivo by early progenitors. Our work provides mechanistic insight into the regulatory landscape underpinning the development of intestinal neural circuits and generates a platform for advancing glial cells as therapeutic agents for the treatment of neural deficits.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
Externí odkaz: