Structurally Conserved Primate LncRNAs Are Transiently Expressed during Human Cortical Differentiation and Influence Cell-Type-Specific Genes.
Animals
Cell Differentiation
/ genetics
Cell Line
Cerebral Cortex
/ physiology
Gene Expression Profiling
/ methods
Gene Expression Regulation
/ genetics
HEK293 Cells
Humans
Organoids
/ physiology
Pluripotent Stem Cells
/ physiology
Primates
RNA, Long Noncoding
/ genetics
Sequence Analysis, RNA
Transcriptome
/ genetics
RNA-seq
brain development
human evolution
induced pluripotent stem cells
lncRNA
neural development
neurogenesis
primate evolution
scRNA-seq
stem cells
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
12 02 2019
12 02 2019
Historique:
received:
06
09
2018
revised:
10
12
2018
accepted:
11
12
2018
pubmed:
15
1
2019
medline:
5
3
2020
entrez:
15
1
2019
Statut:
ppublish
Résumé
The cerebral cortex has expanded in size and complexity in primates, yet the molecular innovations that enabled primate-specific brain attributes remain obscure. We generated cerebral cortex organoids from human, chimpanzee, orangutan, and rhesus pluripotent stem cells and sequenced their transcriptomes at weekly time points for comparative analysis. We used transcript structure and expression conservation to discover gene regulatory long non-coding RNAs (lncRNAs). Of 2,975 human, multi-exonic lncRNAs, 2,472 were structurally conserved in at least one other species and 920 were conserved in all. Three hundred eighty-six human lncRNAs were transiently expressed (TrEx) and many were also TrEx in great apes (46%) and rhesus (31%). Many TrEx lncRNAs are expressed in specific cell types by single-cell RNA sequencing. Four TrEx lncRNAs selected based on cell-type specificity, gene structure, and expression pattern conservation were ectopically expressed in HEK293 cells by CRISPRa. All induced trans gene expression changes were consistent with neural gene regulatory activity.
Identifiants
pubmed: 30639214
pii: S2213-6711(18)30525-3
doi: 10.1016/j.stemcr.2018.12.006
pmc: PMC6372947
pii:
doi:
Substances chimiques
RNA, Long Noncoding
0
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
245-257Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM109031
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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