Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons.
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 ce...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-03-01
|
| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009355&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850239767162126336 |
|---|---|
| author | Jia Li Lei Sun Xue-Liang Peng Xiao-Ming Yu Shao-Jun Qi Zhi John Lu Jing-Dong J Han Qin Shen |
| author_facet | Jia Li Lei Sun Xue-Liang Peng Xiao-Ming Yu Shao-Jun Qi Zhi John Lu Jing-Dong J Han Qin Shen |
| author_sort | Jia Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7dade1f4882f415ca528be26cb60307e |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2021-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-7dade1f4882f415ca528be26cb60307e2025-08-20T02:01:04ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042021-03-01173e100935510.1371/journal.pgen.1009355Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons.Jia LiLei SunXue-Liang PengXiao-Ming YuShao-Jun QiZhi John LuJing-Dong J HanQin ShenNeurogenesis 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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009355&type=printable |
| spellingShingle | Jia Li Lei Sun Xue-Liang Peng Xiao-Ming Yu Shao-Jun Qi Zhi John Lu Jing-Dong J Han Qin Shen Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons. PLoS Genetics |
| title | Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons. |
| title_full | Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons. |
| title_fullStr | Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons. |
| title_full_unstemmed | Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons. |
| title_short | Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons. |
| title_sort | integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and cajal retzius neurons |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009355&type=printable |
| work_keys_str_mv | AT jiali integrativegenomicanalysisofearlyneurogenesisrevealsatemporalgeneticprogramfordifferentiationandspecificationofpreplateandcajalretziusneurons AT leisun integrativegenomicanalysisofearlyneurogenesisrevealsatemporalgeneticprogramfordifferentiationandspecificationofpreplateandcajalretziusneurons AT xueliangpeng integrativegenomicanalysisofearlyneurogenesisrevealsatemporalgeneticprogramfordifferentiationandspecificationofpreplateandcajalretziusneurons AT xiaomingyu integrativegenomicanalysisofearlyneurogenesisrevealsatemporalgeneticprogramfordifferentiationandspecificationofpreplateandcajalretziusneurons AT shaojunqi integrativegenomicanalysisofearlyneurogenesisrevealsatemporalgeneticprogramfordifferentiationandspecificationofpreplateandcajalretziusneurons AT zhijohnlu integrativegenomicanalysisofearlyneurogenesisrevealsatemporalgeneticprogramfordifferentiationandspecificationofpreplateandcajalretziusneurons AT jingdongjhan integrativegenomicanalysisofearlyneurogenesisrevealsatemporalgeneticprogramfordifferentiationandspecificationofpreplateandcajalretziusneurons AT qinshen integrativegenomicanalysisofearlyneurogenesisrevealsatemporalgeneticprogramfordifferentiationandspecificationofpreplateandcajalretziusneurons |