Embryonic vitamin D deficiency programs hematopoietic stem cells to induce type 2 diabetes.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
13 06 2023
13 06 2023
Historique:
received:
13
11
2021
accepted:
19
05
2023
medline:
15
6
2023
pubmed:
14
6
2023
entrez:
13
6
2023
Statut:
epublish
Résumé
Environmental factors may alter the fetal genome to cause metabolic diseases. It is unknown whether embryonic immune cell programming impacts the risk of type 2 diabetes in later life. We demonstrate that transplantation of fetal hematopoietic stem cells (HSCs) made vitamin D deficient in utero induce diabetes in vitamin D-sufficient mice. Vitamin D deficiency epigenetically suppresses Jarid2 expression and activates the Mef2/PGC1a pathway in HSCs, which persists in recipient bone marrow, resulting in adipose macrophage infiltration. These macrophages secrete miR106-5p, which promotes adipose insulin resistance by repressing PIK3 catalytic and regulatory subunits and down-regulating AKT signaling. Vitamin D-deficient monocytes from human cord blood have comparable Jarid2/Mef2/PGC1a expression changes and secrete miR-106b-5p, causing adipocyte insulin resistance. These findings suggest that vitamin D deficiency during development has epigenetic consequences impacting the systemic metabolic milieu.
Identifiants
pubmed: 37311757
doi: 10.1038/s41467-023-38849-z
pii: 10.1038/s41467-023-38849-z
pmc: PMC10264405
doi:
Substances chimiques
Vitamin D
1406-16-2
Mirn106 microRNA, mouse
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3278Subventions
Organisme : BLRD VA
ID : I01 BX003648
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020579
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL094818
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002345
Pays : United States
Informations de copyright
© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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