PMID- 35363520
OWN - NLM
STAT- MEDLINE
DCOM- 20220405
LR  - 20240316
IS  - 2375-2548 (Electronic)
IS  - 2375-2548 (Linking)
VI  - 8
IP  - 13
DP  - 2022 Apr
TI  - Integrated single-cell transcriptomic and epigenetic study of cell state 
      transition and lineage commitment in embryonic mouse cerebellum.
PG  - eabl9156
LID - 10.1126/sciadv.abl9156 [doi]
LID - eabl9156
AB  - Recent studies using single-cell RNA-sequencing 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 trans- and cis-elements that 
      control cell state transition. We reverse engineered gene regulatory networks 
      (GRNs) of each cerebellar cell type. Through in silico simulations and in vivo 
      experiments, we validated the efficacy of GRN analyses and uncovered the 
      molecular control of a posterior transitory zone (PTZ), a distinct progenitor 
      zone residing immediately anterior to the morphologically defined rhombic lip 
      (RL). We showed that perturbing cell fate specification in the PTZ and RL 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.
FAU - Khouri-Farah, Nagham
AU  - Khouri-Farah N
AUID- ORCID: 0000-0002-9849-8905
AD  - Department of Genetics and Genome Sciences, University of Connecticut School of 
      Medicine, 263 Farmington Avenue, Farmington, CT 06030-6403, USA.
FAU - Guo, Qiuxia
AU  - Guo Q
AUID- ORCID: 0000-0002-6687-243X
AD  - Department of Genetics and Genome Sciences, University of Connecticut School of 
      Medicine, 263 Farmington Avenue, Farmington, CT 06030-6403, USA.
FAU - Morgan, Kerry
AU  - Morgan K
AD  - Department of Genetics and Genome Sciences, University of Connecticut School of 
      Medicine, 263 Farmington Avenue, Farmington, CT 06030-6403, USA.
FAU - Shin, Jihye
AU  - Shin J
AD  - Department of Genetics and Genome Sciences, University of Connecticut School of 
      Medicine, 263 Farmington Avenue, Farmington, CT 06030-6403, USA.
FAU - Li, James Y H
AU  - Li JYH
AUID- ORCID: 0000-0002-9231-2698
AD  - Department of Genetics and Genome Sciences, University of Connecticut School of 
      Medicine, 263 Farmington Avenue, Farmington, CT 06030-6403, USA.
AD  - Institute for Systems Genomics, University of Connecticut, 400 Farmington Avenue, 
      Farmington, CT 06030-6403, USA.
LA  - eng
GR  - F31 NS124264/NS/NINDS NIH HHS/United States
GR  - R01 NS106844/NS/NINDS NIH HHS/United States
GR  - R01 NS120556/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20220401
PL  - United States
TA  - Sci Adv
JT  - Science advances
JID - 101653440
SB  - IM
MH  - Animals
MH  - Cell Differentiation/genetics
MH  - Cerebellum/metabolism
MH  - Epigenesis, Genetic
MH  - Mammals/genetics
MH  - Mice
MH  - *Nervous System Malformations/genetics/metabolism
MH  - *Transcriptome
PMC - PMC10938588
EDAT- 2022/04/02 06:00
MHDA- 2022/04/06 06:00
PMCR- 2022/04/01
CRDT- 2022/04/01 17:13
PHST- 2022/04/01 17:13 [entrez]
PHST- 2022/04/02 06:00 [pubmed]
PHST- 2022/04/06 06:00 [medline]
PHST- 2022/04/01 00:00 [pmc-release]
AID - abl9156 [pii]
AID - 10.1126/sciadv.abl9156 [doi]
PST - ppublish
SO  - Sci Adv. 2022 Apr;8(13):eabl9156. doi: 10.1126/sciadv.abl9156. Epub 2022 Apr 1.