Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons

Autoři: Jia Li aff001;  Lei Sun aff004;  Xue-Liang Peng aff003;  Xiao-Ming Yu aff003;  Shao-Jun Qi aff001;  Zhi John Lu aff005;  Jing-Dong J. Han aff006;  Qin Shen aff001
Působiště autorů: Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China aff001;  PTN graduate program, School of Life Sciences, Peking University, Beijing, China aff002;  School of Medicine, Tsinghua University, Beijing, China aff003;  PTN graduate program, School of Life Sciences, Tsinghua University, Beijing, China aff004;  MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing, China aff005;  Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Sh... aff006;  Frontier Science Center for Stem Cell Research, Ministry of Education, School of Life Sciences and Technology, Tongji University, Shanghai, China aff007;  Brain and Spinal Cord Clinical Research Center, Tongji University, Shanghai, China aff008
Vyšlo v časopise: Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons. PLoS Genet 17(3): e1009355. doi:10.1371/journal.pgen.1009355
Kategorie: Research Article


Neurogenesis in the developing neocortex begins with the generation of the preplate, which consists of early-born neurons including Cajal-Retzius (CR) cells and subplate neurons. Here, utilizing the Ebf2-EGFP transgenic mouse in which EGFP initially labels the preplate neurons then persists in CR cells, we reveal the dynamic transcriptome profiles of early neurogenesis and CR cell differentiation. Genome-wide RNA-seq and ChIP-seq analyses at multiple early neurogenic stages have revealed the temporal gene expression dynamics of early neurogenesis and distinct histone modification patterns in early differentiating neurons. We have identified a new set of coding genes and lncRNAs involved in early neuronal differentiation and validated with functional assays in vitro and in vivo. In addition, at E15.5 when Ebf2-EGFP+ cells are mostly CR neurons, single-cell sequencing analysis of purified Ebf2-EGFP+ cells uncovers molecular heterogeneities in CR neurons, but without apparent clustering of cells with distinct regional origins. Along a pseudotemporal trajectory these cells are classified into three different developing states, revealing genetic cascades from early generic neuronal differentiation to late fate specification during the establishment of CR neuron identity and function. Our findings shed light on the molecular mechanisms governing the early differentiation steps during cortical development, especially CR neuron differentiation.

Klíčová slova:

Developmental neuroscience – Gene expression – Histone modification – Hyperexpression techniques – Long non-coding RNA – Neuronal differentiation – Neurons – Stem cells


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