Vascular progenitors generated from tankyrase inhibitor-regulated naïve diabetic human iPSC potentiate efficient revascularization of ischemic retina.
Adult
Animals
Blood Vessels
/ pathology
Cell Differentiation
/ drug effects
Cell Line
Cell Lineage
/ drug effects
Cell Movement
/ drug effects
Cellular Senescence
/ drug effects
DNA Damage
Diabetes Mellitus
/ pathology
Enzyme Inhibitors
/ pharmacology
Epigenesis, Genetic
/ drug effects
Fibroblasts
/ drug effects
Histone Code
Humans
Induced Pluripotent Stem Cells
/ drug effects
Ischemia
/ pathology
Mice
Organoids
/ drug effects
Poly(ADP-ribose) Polymerase Inhibitors
/ pharmacology
Promoter Regions, Genetic
/ genetics
Retina
/ pathology
Stem Cells
/ drug effects
Tankyrases
/ antagonists & inhibitors
Teratoma
/ pathology
Transcription, Genetic
/ drug effects
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
05 03 2020
05 03 2020
Historique:
received:
20
06
2019
accepted:
28
01
2020
entrez:
7
3
2020
pubmed:
7
3
2020
medline:
24
6
2020
Statut:
epublish
Résumé
Here, we report that the functionality of vascular progenitors (VP) generated from normal and disease-primed conventional human induced pluripotent stem cells (hiPSC) can be significantly improved by reversion to a tankyrase inhibitor-regulated human naïve epiblast-like pluripotent state. Naïve diabetic vascular progenitors (N-DVP) differentiated from patient-specific naïve diabetic hiPSC (N-DhiPSC) possessed higher vascular functionality, maintained greater genomic stability, harbored decreased lineage-primed gene expression, and were more efficient in migrating to and re-vascularizing the deep neural layers of the ischemic retina than isogenic diabetic vascular progenitors (DVP). These findings suggest that reprogramming to a stable naïve human pluripotent stem cell state may effectively erase dysfunctional epigenetic donor cell memory or disease-associated aberrations in patient-specific hiPSC. More broadly, tankyrase inhibitor-regulated naïve hiPSC (N-hiPSC) represent a class of human stem cells with high epigenetic plasticity, improved multi-lineage functionality, and potentially high impact for regenerative medicine.
Identifiants
pubmed: 32139672
doi: 10.1038/s41467-020-14764-5
pii: 10.1038/s41467-020-14764-5
pmc: PMC7058090
doi:
Substances chimiques
Enzyme Inhibitors
0
Poly(ADP-ribose) Polymerase Inhibitors
0
Tankyrases
EC 2.4.2.30
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1195Subventions
Organisme : NICHD NIH HHS
ID : R01 HD082098
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL099775
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY009357
Pays : United States
Organisme : NHLBI NIH HHS
ID : R03 HL096220
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY023962
Pays : United States
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