{"doi":"10.1101/2022.09.08.507174","title":"Embryonic Vitamin D Deficiency Programs Hematopoietic Stem Cells to Induce Type 2 Diabetes","abstract":"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 induces 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 subunit alpha and 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":311350,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":329348,"name":"Amy E. Riek","orcid":"0000-0003-4639-1281","position":1,"is_corresponding":false},{"id":708299,"name":"Kevin T. Bauerle","orcid":null,"position":2,"is_corresponding":false},{"id":707729,"name":"Adriana Dusso","orcid":"0000-0002-5108-2929","position":3,"is_corresponding":false},{"id":1007573,"name":"Kyle P. McNerney","orcid":"0000-0003-2874-1014","position":4,"is_corresponding":false},{"id":285046,"name":"Ruteja A. Barve","orcid":"0000-0002-1171-9761","position":5,"is_corresponding":false},{"id":1007942,"name":"Isra Darwech","orcid":null,"position":6,"is_corresponding":false},{"id":791023,"name":"Jennifer Sprague","orcid":"0000-0003-1315-5119","position":7,"is_corresponding":false},{"id":639545,"name":"Clare Moynihan","orcid":null,"position":8,"is_corresponding":false},{"id":1007574,"name":"Rong M. Zhang","orcid":"0000-0002-5764-4363","position":9,"is_corresponding":false},{"id":24564,"name":"Ting Wang","orcid":"0000-0002-6800-242X","position":10,"is_corresponding":false},{"id":233613,"name":"Xiaoyun Xing","orcid":"0000-0002-1045-1775","position":11,"is_corresponding":false},{"id":417526,"name":"Daofeng Li","orcid":"0000-0001-7492-3703","position":12,"is_corresponding":false},{"id":107158,"name":"Richard D. Head","orcid":"0000-0002-6865-1542","position":13,"is_corresponding":false},{"id":353781,"name":"Monika Bambousková","orcid":"0000-0002-8022-4092","position":14,"is_corresponding":false},{"id":1007575,"name":"Marguerite Mrad","orcid":"0000-0002-3293-1438","position":15,"is_corresponding":false},{"id":1007943,"name":"Alejandro Collins","orcid":null,"position":16,"is_corresponding":false},{"id":308934,"name":"Mark S. Sands","orcid":"0000-0002-5559-0832","position":17,"is_corresponding":false},{"id":329356,"name":"Carlos Bernal‐Mizrachi","orcid":"0000-0002-8991-7522","position":18,"is_corresponding":false},{"id":1007941,"name":"Jisu Oh","orcid":null,"position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T00:33:28.480200Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}