Bi-modal reprogramming of cell cycle by MiRNA-4673 amplifies human neurogenic capacity.
Brain
/ cytology
Cell Cycle Checkpoints
/ genetics
Cell Differentiation
/ genetics
Cell Proliferation
/ genetics
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p21
/ metabolism
Cyclin-Dependent Kinases
/ antagonists & inhibitors
Entropy
Humans
MicroRNAs
/ genetics
Neurogenesis
/ genetics
Pericytes
/ metabolism
Receptor, Notch1
/ metabolism
Resting Phase, Cell Cycle
/ genetics
Signal Transduction
/ genetics
Transfection
Tumor Suppressor Protein p53
/ metabolism
MiRNA-4673
cell cycle
differentiation
neurogenesis
Journal
Cell cycle (Georgetown, Tex.)
ISSN: 1551-4005
Titre abrégé: Cell Cycle
Pays: United States
ID NLM: 101137841
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
pubmed:
26
3
2019
medline:
28
5
2020
entrez:
26
3
2019
Statut:
ppublish
Résumé
Molecular mechanisms that inform heterochronic adaptations of neurogenesis in Homo sapiens remain largely unknown. Here, we uncover a signature in the cell cycle that amplifies the proliferative capacity of human neural progenitors by input from microRNA4673 encoded in Notch-1. The miRNA instructs bimodal reprogramming of the cell cycle, leading to initial synchronization of neural precursors at the G0 phase of the cell cycle followed by accelerated progression through interphase. The key event in G0 synchronization is transient inhibition by miR4673 of cyclin-dependent kinase-18, a member of an ancient family of cyclins that license M-G1 transition. In parallel, autophagic degradation of p53/p21 and transcriptional silencing of XRCC3/BRCA2 relax G1/S cell cycle checkpoint and accelerate interphase by ≈2.8-fold. The resultant reprogrammed cell cycle amplifies the proliferative capacity and delays the differentiation of human neural progenitors.
Identifiants
pubmed: 30907228
doi: 10.1080/15384101.2019.1595873
pmc: PMC6527295
doi:
Substances chimiques
CDKN1A protein, human
0
Cyclin-Dependent Kinase Inhibitor p21
0
MIRN4673 microRNA, human
0
MicroRNAs
0
NOTCH1 protein, human
0
Receptor, Notch1
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Cyclin-Dependent Kinases
EC 2.7.11.22
PCTAIRE-3 protein kinase
EC 2.7.11.22
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
848-868Subventions
Organisme : NIDCR NIH HHS
ID : R01 DE015272
Pays : United States
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