{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T19:08:26Z","timestamp":1784056106400,"version":"3.55.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Epigenetic inheritance links fetal chromatin organization and CpG methylation to lifelong tissue phenotypes. We tested the Fetal Chromatin\u2013CpG Developmental Blueprint (FCCD-B) model, proposing that fetal chromatin states shaped by maternal nutrient and transcription factor networks establish regulatory programs preserved in adult traits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated 21\u2009970 fetal single-cell transcriptomes with chromatin accessibility data, including 130 myogenic cells. Adult GWAS datasets included 1614 appendicular lean mass (ALM) loci and 445 grip strength loci. Fine-mapping, colocalization, and gene regulatory networks were inferred using GRNBoost2, Enformer, and Basenji, alongside virtual-cell simulations of nutrient and stress perturbations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ALM and grip strength showed strong genetic correlation (rg\u2009=\u20090.49; Z\u2009=\u200926). Fine-mapping identified 1355 high-confidence ALM loci (median PIP\u2009=\u20090.91). A total of 2935 shared GWAS\u2013eQTL variants overlapped fetal chromatin, with 70\u201388% accessibility preserved in endothelial and cardiomyocyte lineages. A SMAD3-centered TGF-\u03b2 network (50 targets) was identified. Simulations showed that vitamin D, folate, and oxidative stress increased myofibril index (+0.141), epithelial regeneration (+0.035), and combined effects (+0.147).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Persistent fetal chromatin and CpG architectures encode regulatory programs linking maternal environment to adult phenotypes, supporting the FCCD-B model as a predictive framework for developmental epigenetics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/hmg\/ddag062","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T18:38:00Z","timestamp":1784054280000},"source":"Crossref","is-referenced-by-count":0,"title":["Fetal myogenesis chromatin state and CpG from the open alliance markers and their intersection with adult muscle and gastrointestinal genetics"],"prefix":"10.1093","volume":"35","author":[{"given":"Xi","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Stomatology, Hangzhou Linping District Women & Children Hospital , 359 Renmin Avenue, Linping District, Hangzhou 31100 ,","place":["China"]},{"name":"Outpatient Medical Center, Linping Branch, Women's Hospital, School of Medicine, Zhejiang University , 359 Renmin Avenue, Linping District, Hangzhou 31100 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuipei","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, the Fourth Affiliated Hospital of School of Medicine, Zhejiang University , N1 Shangcheng Avenue, Yiwu 32200 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohe","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, the Fourth Affiliated Hospital of School of Medicine, Zhejiang University , N1 Shangcheng Avenue, Yiwu 32200 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5629-1992","authenticated-orcid":false,"given":"Rui","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, the Fourth Affiliated Hospital of School of Medicine, Zhejiang University , N1 Shangcheng Avenue, Yiwu 32200 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"2026071414375025300_ref1","doi-asserted-by":"publisher","first-page":"RP87081","DOI":"10.7554\/eLife.87081","article-title":"Human skeletal muscle organoids model fetal myogenesis and sustain uncommitted PAX7 myogenic progenitors","volume":"12","author":"Mavrommatis","year":"2023","journal-title":"eLife"},{"key":"2026071414375025300_ref2","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1007\/s40618-024-02513-0","article-title":"Insights into pubertal development: a narrative review on the role of epigenetics","volume":"48","author":"Shulhai","year":"2025","journal-title":"J Endocrinol Investig"},{"key":"2026071414375025300_ref3","doi-asserted-by":"publisher","first-page":"31","DOI":"10.12688\/f1000research.159630.3","article-title":"Expression status transition of NOTCH1 accompanies chromatin remodeling in human early retinal progenitor cells","volume":"14","author":"Watabe","year":"2025","journal-title":"F1000Research"},{"key":"2026071414375025300_ref4","doi-asserted-by":"publisher","first-page":"1502778","DOI":"10.3389\/fnana.2024.1502778","article-title":"The histological development of the fetal human inferior colliculus during the second trimester","volume":"18","author":"Nanda","year":"2024","journal-title":"Front Neuroanat"},{"key":"2026071414375025300_ref5","doi-asserted-by":"publisher","volume-title":"Biofluid Dynamics of the Human Maternal\u2013Fetal System","author":"Goyal","DOI":"10.1201\/9781003604310-12"},{"key":"2026071414375025300_ref6","doi-asserted-by":"publisher","first-page":"bvae228","DOI":"10.1210\/jendso\/bvae228","article-title":"Genetics and epigenetics of human pubertal timing: the contribution of genes associated with central precocious puberty","volume":"9","author":"Canton","year":"2025","journal-title":"J Endocr Soc"},{"key":"2026071414375025300_ref7","doi-asserted-by":"publisher","first-page":"e13802","DOI":"10.1111\/cpr.13802","article-title":"Genetically engineered Hypoimmune human muscle progenitor cells can reduce immune rejection","volume":"58","author":"Chen","year":"2025","journal-title":"Cell Prolif"},{"key":"2026071414375025300_ref8","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s13578-024-01339-w","article-title":"Human epicardial organoids from pluripotent stem cells resemble fetal stage with potential cardiomyocyte- transdifferentiation","volume":"15","author":"Wang","year":"2025","journal-title":"Cell Biosci"},{"key":"2026071414375025300_ref9","doi-asserted-by":"publisher","first-page":"e202402819","DOI":"10.26508\/lsa.202402819","article-title":"High-resolution analysis of human centromeric chromatin","volume":"8","author":"Melters","year":"2025","journal-title":"Life Sci Alliance"},{"key":"2026071414375025300_ref10","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1200\/JCO.2025.43.4_suppl.808","article-title":"Association between skeletal muscle morphometrics and overall survival among older adults with gastrointestinal cancers","volume":"43","author":"Doshi","year":"2025","journal-title":"J Clin Oncol"},{"key":"2026071414375025300_ref11","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1200\/JCO.2025.43.4_suppl.834","article-title":"M.CK2 expression gastrointestinal cancer: exploring clinical characteristics and cancer genetics","volume":"43","author":"Wilson","year":"2025","journal-title":"J Clin Oncol"},{"key":"2026071414375025300_ref12","doi-asserted-by":"publisher","first-page":"2410953","DOI":"10.1002\/advs.202410953","article-title":"SYISL knockout promotes embryonic muscle development of offspring by modulating maternal gut microbiota and Fetal myogenic cell dynamics","volume":"12","author":"Zuo","year":"2025","journal-title":"Adv Sci"},{"key":"2026071414375025300_ref13","doi-asserted-by":"publisher","first-page":"e200201","DOI":"10.1212\/NXG.0000000000200201","article-title":"Shared genetics of migraine and gastrointestinal disorders implicates underlying neurologic mechanisms yet heterogeneous Etiologies. Neurology","volume":"10","author":"Chasman","year":"2024","journal-title":"Genetics"},{"key":"2026071414375025300_ref14","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1111\/all.16429","article-title":"Food allergy genetics and epigenetics: a review of genome-wide association studies","volume":"80","author":"Arnau-Soler","year":"2025","journal-title":"Allergy"},{"key":"2026071414375025300_ref15","doi-asserted-by":"publisher","first-page":"e202211073","DOI":"10.1083\/jcb.202211073","article-title":"Single-cell chromatin accessibility profiling reveals a self-renewing muscle satellite cell state","volume":"222","author":"Okafor","year":"2023","journal-title":"J Cell Biol"},{"key":"2026071414375025300_ref16","doi-asserted-by":"publisher","DOI":"10.1101\/2025.01.09.632202","article-title":"Dose-dependent sensitivity of human 3D chromatin to a heart disease-linked transcription factor","author":"Grant","year":"2025"},{"key":"2026071414375025300_ref17","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26020757","article-title":"Highlights of precision medicine, genetics, epigenetics and artificial intelligence in Pompe disease","volume":"26","author":"Moschetti","year":"2025","journal-title":"Int J Mol Sci"},{"key":"2026071414375025300_ref18","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","article-title":"The UK biobank resource with deep phenotyping and genomic data","volume":"562","author":"Bycroft","year":"2018","journal-title":"Nature"},{"key":"2026071414375025300_ref19","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1039\/c3ib40163d","article-title":"Unraveling intestinal stem cell behavior with models of crypt dynamics","volume":"6","author":"Carulli","year":"2014","journal-title":"Integr Biol (Camb)"},{"key":"2026071414375025300_ref20","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1038\/s41540-024-00380-2","article-title":"The art of modeling gene regulatory circuits","volume":"10","author":"G\u00f3mez-Schiavon","year":"2024","journal-title":"NPJ Syst Biol Appl"},{"key":"2026071414375025300_ref21","doi-asserted-by":"publisher","first-page":"3216","DOI":"10.1021\/bi902202q","article-title":"Logic-based models for the analysis of cell Signaling networks","volume":"49","author":"Morris","year":"2010","journal-title":"Biochemistry"},{"key":"2026071414375025300_ref22","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1098\/rsif.2008.0172","article-title":"Approximate Bayesian computation scheme for parameter inference and model selection in dynamical systems","volume":"6","author":"Toni","year":"2009","journal-title":"J R Soc Interface"}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/35\/14\/ddag062\/68780369\/ddag062.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/35\/14\/ddag062\/68780369\/ddag062.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T18:38:00Z","timestamp":1784054280000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/doi\/10.1093\/hmg\/ddag062\/8734209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":22,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2026,6,6]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddag062","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"ddag062"}}