Please use this identifier to cite or link to this item:
Title: A Roadmap for Human Liver Differentiation from Pluripotent Stem Cells
Authors: Ang L.T.
Tan A.K.Y.
Autio M.I. 
Goh S.H., Choo S.H.
Lee K.L. 
Tan J.
Pan B. 
Lee J.J.H.
Lum J.J.
Lim C.Y.Y.
Yeo I.K.X.
Wong C.J.Y.
Liu M.
Oh J.L.L.
Chia C.P.L.
Loh C.H.
Chen A.
Chen Q.
Weissman I.L.
Loh K.M.
Lim B.
Keywords: efficient differentiation
human liver development
pluripotent stem cells
Issue Date: 2018
Publisher: Elsevier B.V.
Citation: Ang L.T., Tan A.K.Y., Autio M.I., Goh S.H., Choo S.H., Lee K.L., Tan J., Pan B., Lee J.J.H., Lum J.J., Lim C.Y.Y., Yeo I.K.X., Wong C.J.Y., Liu M., Oh J.L.L., Chia C.P.L., Loh C.H., Chen A., Chen Q., Weissman I.L., Loh K.M., Lim B. (2018). A Roadmap for Human Liver Differentiation from Pluripotent Stem Cells. Cell Reports 22 (8) : 2190-2205. ScholarBank@NUS Repository.
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-? 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. Ang et al. chart how human liver progenitors develop from pluripotent stem cells through six developmental steps, including extracellular signals and surface markers associated with liver formation. This knowledge enables efficient generation of liver bud progenitors and, subsequently, hepatocyte-like cells that could function in vivo and in vitro. � 2018 The Author(s)
Source Title: Cell Reports
ISSN: 22111247
DOI: 10.1016/j.celrep.2018.01.087
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
PIIS2211124718301517.pdf4.07 MBAdobe PDF




checked on May 27, 2020

Page view(s)

checked on May 21, 2020

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.