{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T08:56:02Z","timestamp":1768467362983,"version":"3.49.0"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1008571","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T00:00:00Z","timestamp":1616025600000}}],"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T00:00:00Z","timestamp":1615161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008982","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMS1562176"],"award-info":[{"award-number":["DMS1562176"]}],"id":[{"id":"10.13039\/501100008982","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008982","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMS1763272"],"award-info":[{"award-number":["DMS1763272"]}],"id":[{"id":"10.13039\/501100008982","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000893","name":"Simons Foundation","doi-asserted-by":"publisher","award":["594598"],"award-info":[{"award-number":["594598"]}],"id":[{"id":"10.13039\/100000893","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01AR073159"],"award-info":[{"award-number":["U01AR073159"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>During early mammalian embryo development, a small number of cells make robust fate decisions at particular spatial locations in a tight time window to form inner cell mass (ICM), and later epiblast (Epi) and primitive endoderm (PE). While recent single-cell transcriptomics data allows scrutinization of heterogeneity of individual cells, consistent spatial and temporal mechanisms the early embryo utilize to robustly form the Epi\/PE layers from ICM remain elusive. Here we build a multiscale three-dimensional model for mammalian embryo to recapitulate the observed patterning process from zygote to late blastocyst. By integrating the spatiotemporal information reconstructed from multiple single-cell transcriptomic datasets, the data-informed modeling analysis suggests two major processes critical to the formation of Epi\/PE layers: a selective cell-cell adhesion mechanism (via EphA4\/EphrinB2) for fate-location coordination and a temporal attenuation mechanism of cell signaling (via Fgf). Spatial imaging data and distinct subsets of single-cell gene expression data are then used to validate the predictions. Together, our study provides a multiscale framework that incorporates single-cell gene expression datasets to analyze gene regulations, cell-cell communications, and physical interactions among cells in complex geometries at single-cell resolution, with direct application to late-stage development of embryogenesis.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1008571","type":"journal-article","created":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T18:40:54Z","timestamp":1615228854000},"page":"e1008571","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["A multiscale model via single-cell transcriptomics reveals robust patterning mechanisms during early mammalian embryo development"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9951-5586","authenticated-orcid":true,"given":"Zixuan","family":"Cang","sequence":"first","affiliation":[]},{"given":"Yangyang","family":"Wang","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2673-921X","authenticated-orcid":true,"given":"Qixuan","family":"Wang","sequence":"additional","affiliation":[]},{"given":"Ken W. Y.","family":"Cho","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6683-4647","authenticated-orcid":true,"given":"William","family":"Holmes","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8804-3368","authenticated-orcid":true,"given":"Qing","family":"Nie","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2021,3,8]]},"reference":[{"issue":"5","key":"pcbi.1008571.ref001","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/S0092-8674(03)00393-3","article-title":"The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells","volume":"113","author":"K. 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