한빛사논문
- 조회474
Jisu Oh 1, Amy E. Riek 1, Kevin T. Bauerle 1,2, Adriana Dusso 1, Kyle P. McNerney 3, Ruteja A. Barve 4, Isra Darwech 1, Jennifer E. Sprague 2, Clare Moynihan 1, Rong M. Zhang 1, Greta Kutz 1, Ting Wang 4, Xiaoyun Xing 4, Daofeng Li 4, Marguerite Mrad 1, Nicholas M. Wigge 1, Esmeralda Castelblanco 1, Alejandro Collin 5, Monika Bambouskova 1, Richard D. Head 4, Mark S. Sands 1,6 & Carlos Bernal-Mizrachi 1,2,6,*
1Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
2Department of Medicine, VA Medical Center, St. Louis, MO, USA.
3Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
4Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
5Instituto de Investigaciones en Ciencias de la Salud (INICSA), CONICET, Universidad Nacional de Córdoba, Córdoba, Argentina.
6Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA.
*Corresponding author: correspondence to Carlos Bernal-Mizrachi
Abstract
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.
논문정보
- Research article
- 2023년 06월 (BRIC 등록일 2023-06-15)
- 국외 연구진
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