6097549
doi
10.5281/zenodo.6097549
oai:zenodo.org:6097549
Guo, Qiuxia
UCHC
Morgan, Kerry
UCHC
Shin, Jihye
UCHC
Li, James
UCHC
Integrated single-cell transcriptomic and epigenetic study of cell-state transition and lineage commitment in embryonic mouse cerebellum
Khouri-Farah, Nagham
UCHC
info:eu-repo/semantics/openAccess
Creative Commons Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/legalcode
<p>Recent studies using single-cell RNA-seq have revealed cellular heterogeneity in the developing mammalian cerebellum, yet the regulatory logic underlying this cellular diversity remains to be elucidated. Using integrated single-cell RNA and ATAC analyses, we resolved developmental trajectories of cerebellar progenitors and identified putative <em>trans</em>- and <em>cis</em>-elements that control cell state transition. We reverse-engineered gene regulatory networks (GRNs) of each cerebellar cell type. Through <em>in silico</em> simulations and <em>in vivo</em> experiments, we validated the efficacy of GRN analyses and uncovered the molecular control of a newly identified stem zone, the posterior transitory zone (PTZ), which contains multipotent progenitors for granule neurons, Bergmann glia, and choroid plexus epithelium. Importantly, we showed that perturbing cell fate specification of PTZ progenitors causes posterior cerebellar vermis hypoplasia, the most common cerebellar birth defect in humans. Our study provides a foundation for comprehensive studies of developmental programs of the mammalian cerebellum</p>
Zenodo
2021-11-11
info:eu-repo/semantics/article
5676084
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21450895
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public
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doi