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dc.contributor.authorAng, Lay Tengen
dc.contributor.authorTan, Antson Kiat Yeeen
dc.contributor.authorAutio, Matias I.en
dc.contributor.authorGoh, Su Huaen
dc.contributor.authorChoo, Siew Huaen
dc.contributor.authorLee, Kian Leongen
dc.contributor.authorTan, Jianminen
dc.contributor.authorPan, Bangfenen
dc.contributor.authorLee, Jane Jia Huien
dc.contributor.authorLum, Jen Jenen
dc.contributor.authorLim, Christina Ying Yanen
dc.contributor.authorYeo, Isabelle Kai Xinen
dc.contributor.authorWong, Chloe Jin Yeeen
dc.contributor.authorLiu, Minen
dc.contributor.authorOh, Jueween Ling Lien
dc.contributor.authorChia, Cheryl Pei Lynnen
dc.contributor.authorLoh, Chet Hongen
dc.contributor.authorChen, Angelaen
dc.contributor.authorChen, Qingfengen
dc.contributor.authorWeissman, Irving L.en
dc.contributor.authorLoh, Kyle M.en
dc.contributor.authorLim, Bingen
dc.identifier.citationAng, L. T., Tan, A. K. Y., Autio, M. I., Goh, S. H., Choo, S. H., Lee, K. L., et al. (2018). A roadmap for human liver differentiation from pluripotent stem cells. Cell Reports, 22(8), 2190-2205.en
dc.description.abstractHow are closely related lineages, including liver, pancreas, and intestines, diversified from a common endodermal origin? Here, we apply principles learned from developmental biology to rapidly reconstitute liver progenitors from human pluripotent stem cells (hPSCs). Mapping the formation of multiple endodermal lineages revealed how alternate endodermal fates (e.g., pancreas and intestines) are restricted during liver commitment. Human liver fate was encoded by combinations of inductive and repressive extracellular signals at different doses. However, these signaling combinations were temporally re-interpreted: cellular competence to respond to retinoid, WNT, TGF-β, and other signals sharply changed within 24 hr. Consequently, temporally dynamic manipulation of extracellular signals was imperative to suppress the production of unwanted cell fates across six consecutive developmental junctures. This efficiently generated 94.1% ± 7.35% TBX3+HNF4A+ human liver bud progenitors and 81.5% ± 3.2% FAH+ hepatocyte-like cells by days 6 and 18 of hPSC differentiation, respectively; the latter improved short-term survival in the Fah−/−Rag2−/−Il2rg−/− mouse model of liver failure.en
dc.description.sponsorshipASTAR (Agency for Sci., Tech. and Research, S’pore)en
dc.format.extent39 p.en
dc.relation.ispartofseriesCell Reportsen
dc.rights© 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (
dc.subjectHuman Liver Developmenten
dc.subjectPluripotent Stem Cellsen
dc.titleA roadmap for human liver differentiation from pluripotent stem cellsen
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen
dc.description.versionPublished versionen
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