期刊
NATURE NEUROSCIENCE
卷 24, 期 1, 页码 34-46出版社
NATURE PORTFOLIO
DOI: 10.1038/s41593-020-00736-x
关键词
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资金
- Swedish Research Council
- Science for Life Laboratory
- Knut and Alice Wallenberg Foundation
- National Genomics Infrastructure - Swedish Research Council
- Swedish Research Council (Vetenskapsradet) [2016-03130]
- Swedish Medical Society
- Ruth and Richard Julin Foundation
- Ollie and Elof Ericssons Foundation
- Magnus Bergvall Foundation
- Brain Foundation (Hjarnfonden)
- Ake Wiberg Foundation
- Wenner-Gren Foundations
- European Research Council [740491]
- Wellcome Trust [200183]
- Karolinska Institutet
- Uppsala Multidisciplinary Center for Advanced Computational Science
- Swedish Research Council, a KAW Scholar and project grant
- Swedish Research Council [2016-03130] Funding Source: Swedish Research Council
- European Research Council (ERC) [740491] Funding Source: European Research Council (ERC)
Utilizing single-cell RNA sequencing, researchers identified 12 enteric neuron classes in the myenteric plexus of the mouse small intestine, revealing a novel principle of neuronal diversification during development. They found that two neuron classes arise through a binary neurogenic branching, while all other identities emerge through subsequent postmitotic differentiation.
Autonomous regulation of the intestine requires the combined activity of functionally distinct neurons of the enteric nervous system (ENS). However, the variety of enteric neuron types and how they emerge during development remain largely unknown. Here, we define a molecular taxonomy of 12 enteric neuron classes within the myenteric plexus of the mouse small intestine using single-cell RNA sequencing. We present cell-cell communication features and histochemical markers for motor neurons, sensory neurons and interneurons, together with transgenic tools for class-specific targeting. Transcriptome analysis of the embryonic ENS uncovers a novel principle of neuronal diversification, where two neuron classes arise through a binary neurogenic branching and all other identities emerge through subsequent postmitotic differentiation. We identify generic and class-specific transcriptional regulators and functionally connect Pbx3 to a postmitotic fate transition. Our results offer a conceptual and molecular resource for dissecting ENS circuits and predicting key regulators for directed differentiation of distinct enteric neuron classes. Imaging and transcriptomic approaches to investigate mouse enteric nervous system diversity and development reveal a new classification of intestinal myenteric neurons and a novel principle of neuronal diversification by postmitotic transitions.
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