{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T18:50:56Z","timestamp":1773687056211,"version":"3.50.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2705700"],"award-info":[{"award-number":["2023YFC2705700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370371"],"award-info":[{"award-number":["82370371"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2025 M772069"],"award-info":[{"award-number":["2025 M772069"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lineage-committed precursors are essential yet rarely identified in mammalian organogenesis, as they lack definitive molecular signatures required for conventional marker-based approaches. Herein, we developed iCommitted, an integrated multi-omics computational pipeline for precise identification of these precursors. iCommitted first reconstructs in vivo organogenesis by modeling the in vitro differentiation trajectory spanning na\u00efve to terminally differentiated cells. It then integrates epigenomic (ATAC-seq\/DNase-seq) and transcriptomic (RNA-seq) data to achieve standardized developmental staging and precursor identification. Applied to mammalian hematopoiesis, iCommitted robustly identified hematopoietic progenitors as the hematopoietic lineage-committed precursors. Subsequent cis-regulatory annotation generated a high-confidence atlas of 16\u00a0774 hematopoietic cis-regulatory elements. Functional analysis of the atlas further pinpointed a 218-bp hematopoietic enhancer (chr6:145\u00a0855\u00a0899-145\u00a0856\u00a0116) that regulates Bhlhe41 expression during lineage commitment. This study establishes a valuable approach for identifying lineage-committed precursors and elucidating regulatory mechanisms in mammalian organogenesis, offering broad utility in developmental biology.<\/jats:p>","DOI":"10.1093\/bib\/bbag114","type":"journal-article","created":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T12:33:41Z","timestamp":1771677221000},"source":"Crossref","is-referenced-by-count":0,"title":["Computational identification of lineage-committed precursors in mammalian organogenesis reveals a novel hematopoietic enhancer regulating\n                    <i>Bhlhe41<\/i>\n                    expression"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9188-7297","authenticated-orcid":false,"given":"Lihui","family":"Jin","sequence":"first","affiliation":[{"name":"Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200092,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenyuan","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology , Beijing 100081,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Hannah","sequence":"additional","affiliation":[{"name":"Department of Haematology and Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge , Cambridge CB2 0XY,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyu","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Gynecology, The First Affiliated Hospital of Ningbo University , Ningbo 315010,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junxin","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200092,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Changhai Hospital, Naval Medical University , Shanghai 200433,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weibin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, People's Hospital of Zhengzhou , Zhengzhou 450053,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Beijing Tongren Hospital, Capital Medical University , Beijing 100730,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200092,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200092,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"2026031613540623700_ref1","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1038\/s41588-022-01018-x","article-title":"Systematic reconstruction of cellular trajectories across mouse embryogenesis","volume":"54","author":"Qiu","year":"2022","journal-title":"Nat Genet"},{"key":"2026031613540623700_ref2","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1038\/s41556-023-01108-w","article-title":"A single-cell transcriptome atlas profiles early organogenesis in human embryos","volume":"25","author":"Xu","year":"2023","journal-title":"Nat Cell Biol"},{"key":"2026031613540623700_ref3","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1038\/s41586-019-0969-x","article-title":"The single-cell transcriptional landscape of mammalian organogenesis","volume":"566","author":"Cao","year":"2019","journal-title":"Nature"},{"key":"2026031613540623700_ref4","doi-asserted-by":"publisher","first-page":"e1700239","DOI":"10.1002\/bies.201700239","article-title":"Identifying human naive pluripotent stem cells\u2014evaluating state-specific reporter lines and cell-surface markers","volume":"40","author":"Collier","year":"2018","journal-title":"Bioessays"},{"key":"2026031613540623700_ref5","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.stem.2010.04.017","article-title":"Pax6 is a human neuroectoderm cell fate determinant","volume":"7","author":"Zhang","year":"2010","journal-title":"Cell Stem Cell"},{"key":"2026031613540623700_ref6","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.joto.2019.03.001","article-title":"Protein biomarkers of neural system","volume":"14","author":"Ghanavatinejad","year":"2019","journal-title":"J Otol"},{"key":"2026031613540623700_ref7","doi-asserted-by":"publisher","first-page":"eadp3957","DOI":"10.1126\/science.adp3957","article-title":"Enhancer-driven cell type comparison reveals similarities between the mammalian and bird pallium","volume":"387","author":"Hecker","year":"2025","journal-title":"Science"},{"key":"2026031613540623700_ref8","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1007\/s10142-023-01185-y","article-title":"Hyper-methylation of ABCG1 as an epigenetics biomarker in non-small cell lung cancer","volume":"23","author":"Tran TO","year":"2023","journal-title":"Funct Integr Genomics"},{"key":"2026031613540623700_ref9","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.3390\/biomedicines9091144","article-title":"Identifying GPSM family members as potential biomarkers in breast cancer: a comprehensive bioinformatics analysis","volume":"9","author":"Dang","year":"2021","journal-title":"Biomedicines"},{"key":"2026031613540623700_ref10","doi-asserted-by":"publisher","first-page":"eaaw3381","DOI":"10.1126\/science.aaw3381","article-title":"Lineage tracing on transcriptional landscapes links state to fate during differentiation","volume":"367","author":"Weinreb","year":"2020","journal-title":"Science"},{"key":"2026031613540623700_ref11","doi-asserted-by":"publisher","first-page":"1062403","DOI":"10.3389\/fcell.2022.1062403","article-title":"Integrated genomic analysis identifies novel low-frequency cis-regulatory variant rs2279658 associated with VSD risk in Chinese children","volume":"10","author":"Jin","year":"2022","journal-title":"Front Cell Dev Biol"},{"key":"2026031613540623700_ref12","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1038\/s41597-024-03272-6","article-title":"Genome-wide profiling of angiogenic cis-regulatory elements unravels cis-regulatory SNPs for vascular abnormality","volume":"11","author":"Jin","year":"2024","journal-title":"Sci Data"},{"key":"2026031613540623700_ref13","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1038\/nrg.2017.57","article-title":"The interplay of epigenetic marks during stem cell differentiation and development","volume":"18","author":"Atlasi","year":"2017","journal-title":"Nat Rev Genet"},{"key":"2026031613540623700_ref14","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/nbt.2859","article-title":"The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells","volume":"32","author":"Trapnell","year":"2014","journal-title":"Nat Biotechnol"},{"key":"2026031613540623700_ref15","doi-asserted-by":"crossref","first-page":"4047","DOI":"10.1038\/ncomms5047","article-title":"Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs","volume":"5","author":"Zhong","year":"2014","journal-title":"Nat Commun"},{"key":"2026031613540623700_ref16","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/s41586-018-0040-3","article-title":"Identification of the tumour transition states occurring during EMT","volume":"556","author":"Pastushenko","year":"2018","journal-title":"Nature"},{"key":"2026031613540623700_ref17","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1242\/dev.040998","article-title":"Embryonic origin of the adult hematopoietic system: advances and questions","volume":"138","author":"Medvinsky","year":"2011","journal-title":"Development"},{"key":"2026031613540623700_ref18","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/j.devcel.2016.01.024","article-title":"Dynamic gene regulatory networks drive hematopoietic specification and differentiation","volume":"36","author":"Goode","year":"2016","journal-title":"Dev Cell"},{"key":"2026031613540623700_ref19","doi-asserted-by":"publisher","first-page":"D1117","DOI":"10.1093\/nar\/gku895","article-title":"Codex: a next-generation sequencing experiment database for the haematopoietic and embryonic stem cell communities","volume":"43","author":"Sanchez-Castillo","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2026031613540623700_ref20","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/s41576-019-0173-8","article-title":"Determinants of enhancer and promoter activities of regulatory elements","volume":"21","author":"Andersson","year":"2020","journal-title":"Nat Rev Genet"},{"key":"2026031613540623700_ref21","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.jgg.2023.09.005","article-title":"The evolving views of hematopoiesis: from embryo to adulthood and from in vivo to in vitro","volume":"51","author":"Zhang","year":"2024","journal-title":"J Genet Genomics"},{"key":"2026031613540623700_ref22","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1038\/ni.3694","article-title":"Essential role for the transcription factor Bhlhe41 in regulating the development, self-renewal and BCR repertoire of B-1a cells","volume":"18","author":"Kreslavsky","year":"2017","journal-title":"Nat Immunol"},{"key":"2026031613540623700_ref23","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1101\/gr.190595.115","article-title":"Defining cell types and states with single-cell genomics","volume":"25","author":"Trapnell","year":"2015","journal-title":"Genome Res"},{"key":"2026031613540623700_ref24","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1038\/nbt.3711","article-title":"Revealing the vectors of cellular identity with single-cell genomics","volume":"34","author":"Wagner","year":"2016","journal-title":"Nat Biotechnol"},{"key":"2026031613540623700_ref25","doi-asserted-by":"publisher","first-page":"e21","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive integration of single-cell data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"2026031613540623700_ref26","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/nrg3458","article-title":"Enhancers: five essential questions","volume":"14","author":"Pennacchio","year":"2013","journal-title":"Nat Rev Genet"},{"key":"2026031613540623700_ref27","doi-asserted-by":"publisher","first-page":"eaay5247","DOI":"10.1126\/sciadv.aay5247","article-title":"Chromatin accessibility analysis reveals regulatory dynamics of developing human retina and hiPSC-derived retinal organoids","volume":"6","author":"Xie","year":"2020","journal-title":"Sci Adv"},{"key":"2026031613540623700_ref28","doi-asserted-by":"publisher","first-page":"D324","DOI":"10.1093\/nar\/gkae940","article-title":"VISTA enhancer browser: an updated database of tissue-specific developmental enhancers","volume":"53","author":"Kosicki","year":"2025","journal-title":"Nucleic Acids Res"},{"key":"2026031613540623700_ref29","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang da","year":"2009","journal-title":"Nat Protoc"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/27\/2\/bbag114\/67371369\/bbag114.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/27\/2\/bbag114\/67371369\/bbag114.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T17:54:12Z","timestamp":1773683652000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbag114\/8524999"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,1]]},"references-count":29,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,3,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbag114","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3]]},"published":{"date-parts":[[2026,3,1]]},"article-number":"bbag114"}}