TY - JOUR
T1 - Differentiation of hepatocyte-like cells from human pluripotent stem cells using small molecules
AU - Asumda, Faizal Z.
AU - Hatzistergos, Konstantinos E.
AU - Dykxhoorn, Derek M.
AU - Jakubski, Silvia
AU - Edwards, Jasmine
AU - Thomas, Emmanuel
AU - Schiff, Eugene R.
N1 - Publisher Copyright:
© 2018 International Society of Differentiation
PY - 2018/5/1
Y1 - 2018/5/1
N2 - A variety of approaches have been developed for the derivation of hepatocyte-like cells from pluripotent stem cells. Currently, most of these strategies employ step-wise differentiation approaches with recombinant growth-factors or small-molecule analogs to recapitulate developmental signaling pathways. Here, we tested the efficacy of a small-molecule based differentiation protocol for the generation of hepatocyte-like cells from human pluripotent stem cells. Quantitative gene-expression, immunohistochemical, and western blot analyses for SOX17, FOXA2, CXCR4, HNF4A, AFP, indicated the stage-specific differentiation into definitive endoderm, hepatoblast and hepatocyte-like derivatives. Furthermore, hepatocyte-like cells displayed morphological and functional features characteristic of primary hepatocytes, as indicated by the production of ALB (albumin) and α-1-antitrypsin (A1AT), as well as glycogen storage capacity by periodic acid-Schiff staining. Together, these data support that the small-molecule based hepatic differentiation protocol is a simple, reproducible, and inexpensive method to efficiently drive the differentiation of human pluripotent stem cells towards a hepatocyte-like phenotype, for downstream pharmacogenomic and regenerative medicine applications.
AB - A variety of approaches have been developed for the derivation of hepatocyte-like cells from pluripotent stem cells. Currently, most of these strategies employ step-wise differentiation approaches with recombinant growth-factors or small-molecule analogs to recapitulate developmental signaling pathways. Here, we tested the efficacy of a small-molecule based differentiation protocol for the generation of hepatocyte-like cells from human pluripotent stem cells. Quantitative gene-expression, immunohistochemical, and western blot analyses for SOX17, FOXA2, CXCR4, HNF4A, AFP, indicated the stage-specific differentiation into definitive endoderm, hepatoblast and hepatocyte-like derivatives. Furthermore, hepatocyte-like cells displayed morphological and functional features characteristic of primary hepatocytes, as indicated by the production of ALB (albumin) and α-1-antitrypsin (A1AT), as well as glycogen storage capacity by periodic acid-Schiff staining. Together, these data support that the small-molecule based hepatic differentiation protocol is a simple, reproducible, and inexpensive method to efficiently drive the differentiation of human pluripotent stem cells towards a hepatocyte-like phenotype, for downstream pharmacogenomic and regenerative medicine applications.
KW - Hepatocyte
KW - Hepatocyte-like cells
KW - Human pluripotent stem cell differentiation
KW - Small molecules
UR - http://www.scopus.com/inward/record.url?scp=85044964852&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044964852&partnerID=8YFLogxK
U2 - 10.1016/j.diff.2018.03.002
DO - 10.1016/j.diff.2018.03.002
M3 - Article
C2 - 29626713
AN - SCOPUS:85044964852
SN - 0301-4681
VL - 101
SP - 16
EP - 24
JO - Differentiation
JF - Differentiation
ER -