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Title: A roadmap for human liver differentiation from pluripotent stem cells
Authors: Ang, Lay Teng
Tan, Antson Kiat Yee
Autio, Matias I.
Goh, Su Hua
Choo, Siew Hua
Lee, Kian Leong
Tan, Jianmin
Pan, Bangfen
Lee, Jane Jia Hui
Lum, Jen Jen
Lim, Christina Ying Yan
Yeo, Isabelle Kai Xin
Wong, Chloe Jin Yee
Liu, Min
Oh, Jueween Ling Li
Chia, Cheryl Pei Lynn
Loh, Chet Hong
Chen, Angela
Chen, Qingfeng
Weissman, Irving L.
Loh, Kyle M.
Lim, Bing
Keywords: Human Liver Development
Pluripotent Stem Cells
Issue Date: 2018
Source: Ang, 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.
Series/Report no.: Cell Reports
Abstract: How 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.
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2018.01.087
Rights: © 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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