Please use this identifier to cite or link to this item: https://doi.org/10.1101/174698
Title: Accelerated human liver progenitor generation from pluripotent stem cells by inhibiting formation of unwanted lineages
Authors: Lay Teng Ang
Antson Kiat Yee Tan
Matias Ilmari Autio 
Joanne Su-Hua Goh
Siew Hua Choo 
Kian Leong Lee 
Jianmin Tan
Bangfen Pan 
Jane Jia Hui Lee
Isabelle Kai Xin Yeo
Chloe Jin Yee Wong
Jen Jen Lum
Chet Hong Loh
Ying Yan Lim
Jueween Ling Li Oh
Cheryl Pei Lynn Chia
Angela Chen
Qing Feng Chen 
Irving L. Weissman
Kyle M. Loh
Bing Lim
Issue Date: 2017
Citation: Lay Teng Ang, Antson Kiat Yee Tan, Matias Ilmari Autio, Joanne Su-Hua Goh, Siew Hua Choo, Kian Leong Lee, Jianmin Tan, Bangfen Pan, Jane Jia Hui Lee, Isabelle Kai Xin Yeo, Chloe Jin Yee Wong, Jen Jen Lum, Chet Hong Loh, Ying Yan Lim, Jueween Ling Li Oh, Cheryl Pei Lynn Chia, Angela Chen, Qing Feng Chen, Irving L. Weissman, Kyle M. Loh, Bing Lim (2017). Accelerated human liver progenitor generation from pluripotent stem cells by inhibiting formation of unwanted lineages. BioRxiv : 174698. ScholarBank@NUS Repository. https://doi.org/10.1101/174698
Rights: Attribution 4.0 International
Abstract: Despite decisive progress in differentiating pluripotent stem cells (PSCs) into diverse cell-types, the often-lengthy differentiation and functional immaturity of such cell-types remain pertinent issues. Here we address the first challenge of prolonged differentiation in the generation of hepatocyte-like cells from PSCs. We delineate a roadmap describing the extracellular signals controlling six sequential branching lineage choices leading from pluripotency to endoderm, foregut, and finally, liver progenitors. By blocking formation of unwanted cell-types at each lineage juncture and manipulating temporally-dynamic signals, we accelerated generation of 89.0�3.1% AFP+�human liver bud progenitors and 87.3�9.4% ALBUMIN+�hepatocyte-like cells by days 6 and 18 of PSC differentiation, respectively. 81.5�3.2% of hepatocyte-like cells expressed metabolic enzyme FAH (as assayed by a new knock-in reporter line) and improved short-term survival in the�Fah-/-Rag2-/-Il2rg-/-�mouse model of liver failure. Collectively the timed signaling interventions indicated by this developmental roadmap enable accelerated production of human liver progenitors from PSCs.
Source Title: BioRxiv
URI: https://scholarbank.nus.edu.sg/handle/10635/164271
DOI: 10.1101/174698
Rights: Attribution 4.0 International
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