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Publication : Single-cell chromatin accessibility identifies enhancer networks driving gene expression during spinal cord development in mouse.

First Author  Shu M Year  2022
Journal  Dev Cell Volume  57
Issue  24 Pages  2761-2775.e6
PubMed ID  36495874 Mgi Jnum  J:332270
Mgi Id  MGI:7413814 Doi  10.1016/j.devcel.2022.11.011
Citation  Shu M, et al. (2022) Single-cell chromatin accessibility identifies enhancer networks driving gene expression during spinal cord development in mouse. Dev Cell 57(24):2761-2775.e6
abstractText  Spinal cord development is precisely orchestrated by spatiotemporal gene regulatory programs. However, the underlying epigenetic mechanisms remain largely elusive. Here, we profiled single-cell chromatin accessibility landscapes in mouse neural tubes spanning embryonic days 9.5-13.5. We identified neuronal-cell-cluster-specific cis-regulatory elements in neural progenitors and neurons. Furthermore, we applied a novel computational method, eNet, to build enhancer networks by integrating single-cell chromatin accessibility and gene expression data and identify the hub enhancers within enhancer networks. It was experimentally validated in vivo for Atoh1 that knockout of the hub enhancers, but not the non-hub enhancers, markedly decreased Atoh1 expression and reduced dp1/dI1 cells. Together, our work provides insights into the epigenetic regulation of spinal cord development and a proof-of-concept demonstration of enhancer networks as a general mechanism in transcriptional regulation.
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