LRIG1 is a gatekeeper to exit from quiescence in adult neural stem cells.
Adult Stem Cells
/ cytology
Animals
Bone Morphogenetic Protein 4
/ pharmacology
Cell Cycle
/ genetics
Cell Cycle Proteins
/ metabolism
Cell Proliferation
/ genetics
DNA-Binding Proteins
/ metabolism
ErbB Receptors
/ pharmacology
Fibroblast Growth Factor 2
/ pharmacology
Gene Ontology
Immunohistochemistry
Interferons
/ pharmacology
Lateral Ventricles
/ cytology
MAP Kinase Signaling System
/ drug effects
Membrane Glycoproteins
/ genetics
Mice
Nerve Tissue Proteins
/ genetics
Neural Stem Cells
/ cytology
Neurogenesis
/ genetics
Proteomics
RNA-Seq
Regeneration
/ drug effects
Tetraspanin 29
/ metabolism
Up-Regulation
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 05 2021
10 05 2021
Historique:
received:
20
12
2019
accepted:
26
03
2021
entrez:
11
5
2021
pubmed:
12
5
2021
medline:
3
6
2021
Statut:
epublish
Résumé
Adult neural stem cells (NSCs) must tightly regulate quiescence and proliferation. Single-cell analysis has suggested a continuum of cell states as NSCs exit quiescence. Here we capture and characterize in vitro primed quiescent NSCs and identify LRIG1 as an important regulator. We show that BMP-4 signaling induces a dormant non-cycling quiescent state (d-qNSCs), whereas combined BMP-4/FGF-2 signaling induces a distinct primed quiescent state poised for cell cycle re-entry. Primed quiescent NSCs (p-qNSCs) are defined by high levels of LRIG1 and CD9, as well as an interferon response signature, and can efficiently engraft into the adult subventricular zone (SVZ) niche. Genetic disruption of Lrig1 in vivo within the SVZ NSCs leads an enhanced proliferation. Mechanistically, LRIG1 primes quiescent NSCs for cell cycle re-entry and EGFR responsiveness by enabling EGFR protein levels to increase but limiting signaling activation. LRIG1 is therefore an important functional regulator of NSC exit from quiescence.
Identifiants
pubmed: 33972529
doi: 10.1038/s41467-021-22813-w
pii: 10.1038/s41467-021-22813-w
pmc: PMC8110534
doi:
Substances chimiques
Bmp4 protein, mouse
0
Bone Morphogenetic Protein 4
0
Cd9 protein, mouse
0
Cell Cycle Proteins
0
DNA-Binding Proteins
0
Lrig1 protein, mouse
0
Membrane Glycoproteins
0
Nerve Tissue Proteins
0
Ris2 protein, mouse
0
Tetraspanin 29
0
Fibroblast Growth Factor 2
103107-01-3
Interferons
9008-11-1
EGFR protein, mouse
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2594Subventions
Organisme : Cancer Research UK
ID : A19778
Pays : United Kingdom
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