A branching model of lineage differentiation underpinning the neurogenic potential of enteric glia
Abstract 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 cell...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41492-3 |
| _version_ | 1797557817237831680 |
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| author | Anna Laddach Song Hui Chng Reena Lasrado Fränze Progatzky Michael Shapiro Alek Erickson Marisol Sampedro Castaneda Artem V. Artemov Ana Carina Bon-Frauches Eleni-Maria Amaniti Jens Kleinjung Stefan Boeing Sila Ultanir Igor Adameyko Vassilis Pachnis |
| author_facet | Anna Laddach Song Hui Chng Reena Lasrado Fränze Progatzky Michael Shapiro Alek Erickson Marisol Sampedro Castaneda Artem V. Artemov Ana Carina Bon-Frauches Eleni-Maria Amaniti Jens Kleinjung Stefan Boeing Sila Ultanir Igor Adameyko Vassilis Pachnis |
| author_sort | Anna Laddach |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-10T17:22:33Z |
| format | Article |
| id | doaj.art-86392e391ca64dc18dbed188143dce59 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:22:33Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-86392e391ca64dc18dbed188143dce592023-11-20T10:18:14ZengNature PortfolioNature Communications2041-17232023-09-0114112010.1038/s41467-023-41492-3A branching model of lineage differentiation underpinning the neurogenic potential of enteric gliaAnna Laddach0Song Hui Chng1Reena Lasrado2Fränze Progatzky3Michael Shapiro4Alek Erickson5Marisol Sampedro Castaneda6Artem V. Artemov7Ana Carina Bon-Frauches8Eleni-Maria Amaniti9Jens Kleinjung10Stefan Boeing11Sila Ultanir12Igor Adameyko13Vassilis Pachnis14Nervous System Development and Homeostasis Laboratory, the Francis Crick InstituteNervous System Development and Homeostasis Laboratory, the Francis Crick InstituteNervous System Development and Homeostasis Laboratory, the Francis Crick InstituteNervous System Development and Homeostasis Laboratory, the Francis Crick InstituteNervous System Development and Homeostasis Laboratory, the Francis Crick InstituteDepartment of Physiology and Pharmacology, Karolinska InstitutetKinases and Brain Development Laboratory, the Francis Crick InstituteDepartment of Neuroimmunology, Center for Brain Research, Medical University of ViennaNervous System Development and Homeostasis Laboratory, the Francis Crick InstituteNervous System Development and Homeostasis Laboratory, the Francis Crick InstituteNervous System Development and Homeostasis Laboratory, the Francis Crick InstituteBioinformatics and Biostatistics Science Technology Platform, the Francis Crick InstituteKinases and Brain Development Laboratory, the Francis Crick InstituteDepartment of Physiology and Pharmacology, Karolinska InstitutetNervous System Development and Homeostasis Laboratory, the Francis Crick InstituteAbstract 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.https://doi.org/10.1038/s41467-023-41492-3 |
| spellingShingle | Anna Laddach Song Hui Chng Reena Lasrado Fränze Progatzky Michael Shapiro Alek Erickson Marisol Sampedro Castaneda Artem V. Artemov Ana Carina Bon-Frauches Eleni-Maria Amaniti Jens Kleinjung Stefan Boeing Sila Ultanir Igor Adameyko Vassilis Pachnis A branching model of lineage differentiation underpinning the neurogenic potential of enteric glia Nature Communications |
| title | A branching model of lineage differentiation underpinning the neurogenic potential of enteric glia |
| title_full | A branching model of lineage differentiation underpinning the neurogenic potential of enteric glia |
| title_fullStr | A branching model of lineage differentiation underpinning the neurogenic potential of enteric glia |
| title_full_unstemmed | A branching model of lineage differentiation underpinning the neurogenic potential of enteric glia |
| title_short | A branching model of lineage differentiation underpinning the neurogenic potential of enteric glia |
| title_sort | branching model of lineage differentiation underpinning the neurogenic potential of enteric glia |
| url | https://doi.org/10.1038/s41467-023-41492-3 |
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