Origins and Proliferative States of Human Oligodendrocyte Precursor Cells.
Cadherin Related Proteins
Cadherins
/ genetics
Cell Proliferation
/ genetics
Cells, Cultured
Cerebral Cortex
/ cytology
Ependymoglial Cells
/ cytology
ErbB Receptors
/ genetics
HEK293 Cells
Humans
Immunohistochemistry
Neurogenesis
/ genetics
Oligodendrocyte Precursor Cells
/ cytology
RNA, Small Interfering
RNA-Seq
Single-Cell Analysis
White Matter
/ cytology
EGFR
OPC
PCDH15
cortical expansion
oligodendrogenesis
self-repulsion
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
06 08 2020
06 08 2020
Historique:
received:
23
08
2019
revised:
22
04
2020
accepted:
16
06
2020
pubmed:
18
7
2020
medline:
30
3
2021
entrez:
18
7
2020
Statut:
ppublish
Résumé
Human cerebral cortex size and complexity has increased greatly during evolution. While increased progenitor diversity and enhanced proliferative potential play important roles in human neurogenesis and gray matter expansion, the mechanisms of human oligodendrogenesis and white matter expansion remain largely unknown. Here, we identify EGFR-expressing "Pre-OPCs" that originate from outer radial glial cells (oRGs) and undergo mitotic somal translocation (MST) during division. oRG-derived Pre-OPCs provide an additional source of human cortical oligodendrocyte precursor cells (OPCs) and define a lineage trajectory. We further show that human OPCs undergo consecutive symmetric divisions to exponentially increase the progenitor pool size. Additionally, we find that the OPC-enriched gene, PCDH15, mediates daughter cell repulsion and facilitates proliferation. These findings indicate properties of OPC derivation, proliferation, and dispersion important for human white matter expansion and myelination.
Identifiants
pubmed: 32679030
pii: S0092-8674(20)30759-5
doi: 10.1016/j.cell.2020.06.027
pmc: PMC7415734
mid: NIHMS1606280
pii:
doi:
Substances chimiques
CDHR15, human
0
Cadherin Related Proteins
0
Cadherins
0
RNA, Small Interfering
0
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
594-608.e11Subventions
Organisme : Medical Research Council
ID : MC_PC_17230
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : P01 NS083513
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS097305
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH105989
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS075998
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_12009
Pays : United Kingdom
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests A.R.K. is a co-founder and board member of Neurona Therapeutics.
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