Optimal Hypoxia Regulates Human iPSC-Derived Liver Bud Differentiation through Intercellular TGFB Signaling

Stem Cell Reports
Hiroaki AyabeHideki Taniguchi

Abstract

Timely controlled oxygen (O2) delivery is crucial for the developing liver. However, the influence of O2 on intercellular communication during hepatogenesis is unclear. Using a human induced pluripotent stem cell-derived liver bud (hiPSC-LB) model, we found hypoxia induced with an O2-permeable plate promoted hepatic differentiation accompanied by TGFB1 and TGFB3 suppression. Conversely, extensive hypoxia generated with an O2-non-permeable plate elevated TGFBs and cholangiocyte marker expression. Single-cell RNA sequencing revealed that TGFB1 and TGFB3 are primarily expressed in the human liver mesenchyme and endothelium similar to in the hiPSC-LBs. Stromal cell-specific RNA interferences indicated the importance of TGFB signaling for hepatocytic differentiation in hiPSC-LB. Consistently, during mouse liver development, the Hif1a-mediated developmental hypoxic response is positively correlated with TGFB1 expression. These data provide insights into the mechanism that hypoxia-stimulated signals in mesenchyme and endothelium, likely through TGFB1, promote hepatoblast differentiation prior to fetal circulation establishment.

References

Dec 24, 2005·Kidney International·W M BernhardtK-U Eckardt
Dec 26, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Lananh N NguyenW Tony Parks
Feb 24, 2009·Nature Reviews. Molecular Cell Biology·Hellmut G AugustinKari Alitalo
Jan 12, 2010·Developmental Cell·Sally L Dunwoodie
Jul 24, 2010·EMBO Molecular Medicine·Friederike BöhmSabine Werner
Jul 18, 2012·Proceedings of the National Academy of Sciences of the United States of America·Masatoshi KajiwaraShinya Yamanaka
Oct 9, 2012·Mechanisms of Development·Daisuke SugiyamaChiyo Mizuochi
Oct 23, 2012·Journal of the American Society of Nephrology : JASN·Christodoulos XinarisGiuseppe Remuzzi
Jul 19, 2014·Science·Madeline A Lancaster, Juergen A Knoblich
Oct 6, 2014·Trends in Biotechnology·Matthew B ByrnePaul J A Kenis
Oct 20, 2014·Nature Medicine·Carey L WatsonMichael A Helmrath
Jun 18, 2015·Development·Miriam GordilloValerie Gouon-Evans
Sep 28, 2016·Developmental Cell·Kai Kretzschmar, Hans Clevers

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Citations

Jun 12, 2019·Pediatric Research·Bethany N Radford, Victor K M Han
Jul 23, 2019·Tissue Engineering. Part C, Methods·Michael A PhelanPeter I Lelkes
Apr 15, 2020·Scientific Reports·Nobuhito MoriYasuyuki S Kida
May 10, 2020·Journal of Neural Transmission·Philipp WörsdörferSüleyman Ergün
Dec 19, 2020·Antioxidants & Redox Signaling·Philipp Wörsdörfer, Süleyman Ergün
Mar 9, 2021·Frontiers in Immunology·Soumya R MohapatraChristiane A Opitz
Mar 26, 2021·Seminars in Liver Disease·Haichuan WangXin Chen

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Datasets Mentioned

BETA
GSE96981

Methods Mentioned

BETA
delamination
FACS
fluorescence-activated cell sorting
ELISA

Software Mentioned

ImageJ

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