{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T03:12:37Z","timestamp":1793502757303,"version":"4.5.0"},"posted":{"date-parts":[[2025,10,6]]},"group-title":"Genomics","reference-count":27,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["F30 HD106744"],"award-info":[{"award-number":["F30 HD106744"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation Korea","doi-asserted-by":"crossref","award":["NRF-2020R1A3B2078973"],"award-info":[{"award-number":["NRF-2020R1A3B2078973"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Korea Health Technology R&D Project","award":["RS-2024-00440005"],"award-info":[{"award-number":["RS-2024-00440005"]}]},{"name":"Suh Kyungbae Foundation","award":["SUHF-18010082"],"award-info":[{"award-number":["SUHF-18010082"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Monozygotic twins are derived from the split of a single zygote early in embryogenesis. Although it was hypothesized that the timing of twining is overall associated with fetal membrane configuration of twins, i.e., chorionicity and amnionicity, our understanding of early embryonic clonal dynamics underlying human twinning is limited. Here we explored the segregations of early embryonic lineages in 7 dichorionic diamniotic (\n                  <jats:bold>DCDA<\/jats:bold>\n                  ), 7 monochorionic diamniotic (\n                  <jats:bold>MCDA<\/jats:bold>\n                  ), 8 monochorionic monoamniotic (\n                  <jats:bold>MCMA<\/jats:bold>\n                  ) monozygotic twins, and 1 dichorionic triamniotic (\n                  <jats:bold>DCTA<\/jats:bold>\n                  ) monozygotic triplets, using post-zygotic early embryonic mutations (\n                  <jats:bold>EEMs<\/jats:bold>\n                  ) as endogenous lineage barcodes. Patterns of the early lineage distributions among monozygotic twins revealed three apparent clonal categories, referred to as para-identical, sub-identical, and full-identical twins, which largely correlated with the amnionicity of the twins. Rather, despite conventional wisdom, chorionicity was not substantially associated with early clonal compositions, but with blood exchanges\n                  <jats:italic>in utero<\/jats:italic>\n                  . In sub-identical twins, where one co-twin was clonally a part of the other, our data suggested that the foundation of the latter co-twin was established after acquisition of a median of 6 additional post-zygotic mutations (range: 2\u201313), corresponding to \u223c5 early cell divisions. Additional\n                  <jats:italic>in-depth<\/jats:italic>\n                  analysis on the matched placenta from an MCDA twin suggested that separation of two co-twins can precede the separation of the placenta and embryonic proper, and a single chorion can be formed even with multiclonal origin. Our findings provide insights into the clonal dynamics, twinning processes, and cell fate decisions in early human embryogenesis.\n                <\/jats:p>","DOI":"10.1101\/2025.10.05.680569","type":"posted-content","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:20:13Z","timestamp":1759796413000},"source":"Crossref","is-referenced-by-count":1,"title":["Clonal dynamics of monozygotic twinning in early human embryogenesis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5714-7087","authenticated-orcid":false,"given":"Christopher Jongsoo","family":"Yoon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang Hyun","family":"Nam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Mi","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Saem","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hye","family":"Bae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haemin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Mi","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joonoh","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryul","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Derom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline","family":"Meireson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Weyers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Woo","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junehawk","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5514-4189","authenticated-orcid":false,"given":"Joohon","family":"Sung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0843-4271","authenticated-orcid":false,"given":"Obi L.","family":"Griffith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malachi","family":"Griffith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Kwan","family":"Jun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Seok","family":"Ju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025101002250797000_2025.10.05.680569v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3441"},{"key":"2025101002250797000_2025.10.05.680569v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13448"},{"key":"2025101002250797000_2025.10.05.680569v1.3","doi-asserted-by":"publisher","DOI":"10.1086\/302502"},{"key":"2025101002250797000_2025.10.05.680569v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03790-y"},{"key":"2025101002250797000_2025.10.05.680569v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03345-1"},{"key":"2025101002250797000_2025.10.05.680569v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(55)90001-6"},{"key":"2025101002250797000_2025.10.05.680569v1.7","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-102197"},{"key":"2025101002250797000_2025.10.05.680569v1.8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.082089499"},{"key":"2025101002250797000_2025.10.05.680569v1.9","doi-asserted-by":"crossref","first-page":"60","DOI":"10.5966\/sctm.2016-0110","article-title":"Concise Review: Hematopoietic Stem Cell Origins: Lessons from Embryogenesis for Improving Regenerative Medicine","volume":"6","year":"2017","journal-title":"Stem Cells Transl Med"},{"key":"2025101002250797000_2025.10.05.680569v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14237-7"},{"key":"2025101002250797000_2025.10.05.680569v1.11","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1017\/S0967199413000257","article-title":"The timing of monozygotic twinning: a criticism of the common model","volume":"23","year":"2015","journal-title":"Zygote"},{"key":"2025101002250797000_2025.10.05.680569v1.12","doi-asserted-by":"publisher","DOI":"10.1126\/science.1150648"},{"key":"2025101002250797000_2025.10.05.680569v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-00755-1"},{"key":"2025101002250797000_2025.10.05.680569v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/nature21703"},{"key":"2025101002250797000_2025.10.05.680569v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2008.03.050"},{"key":"2025101002250797000_2025.10.05.680569v1.16","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.ajog.2015.10.930","article-title":"A review of the mechanisms and evidence for typical and atypical twinning","volume":"214","year":"2016","journal-title":"Am J Obstet Gynecol"},{"key":"2025101002250797000_2025.10.05.680569v1.17","first-page":"562","article-title":"Complete human day 14 post-implantation embryo models from naive ES cells","volume":"622","year":"2023","journal-title":"Nature"},{"key":"2025101002250797000_2025.10.05.680569v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03786-8"},{"key":"2025101002250797000_2025.10.05.680569v1.19","doi-asserted-by":"publisher","DOI":"10.1242\/dev.183095"},{"key":"2025101002250797000_2025.10.05.680569v1.20","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/s41586-025-08922-2","article-title":"Human de novo mutation rates from a four-generation pedigree reference","volume":"643","year":"2025","journal-title":"Nature"},{"key":"2025101002250797000_2025.10.05.680569v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3469"},{"key":"2025101002250797000_2025.10.05.680569v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01793-4"},{"key":"2025101002250797000_2025.10.05.680569v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/nature07943"},{"key":"2025101002250797000_2025.10.05.680569v1.24","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0910752"},{"key":"2025101002250797000_2025.10.05.680569v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.05.003"},{"key":"2025101002250797000_2025.10.05.680569v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.159"},{"key":"2025101002250797000_2025.10.05.680569v1.27","first-page":"100301","article-title":"Whole-genome sequences reveal zygotic composition in chimeric twins","volume":"5","year":"2024","journal-title":"HGG Adv"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.10.05.680569","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:45:06Z","timestamp":1768470306000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.10.05.680569"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,6]]},"references-count":27,"URL":"https:\/\/doi.org\/10.1101\/2025.10.05.680569","relation":{},"subject":[],"published":{"date-parts":[[2025,10,6]]},"subtype":"preprint"}}