Human hepatic organoids for the analysis of human genetic diseases
Yuan Guan, Dan Xu, Phillip M. Garfin, Ursula Ehmer, Melissa Hurwitz, Greg Enns, Sara Michie, Manhong Wu, Ming Zheng, Toshihiko Nishimura, Julien Sage, and Gary Peltz
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Published October 23, 2023 - More info
JCI Insight. 2023;8(20):e176034. https://doi.org/10.1172/jci.insight.176034.
© 2023 The American Society for Clinical Investigation
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Abstract
We developed an in vitro model system where induced pluripotent stem cells (iPSCs) differentiate into 3-dimensional human hepatic organoids (HOs) through stages that resemble human liver during its embryonic development. The HOs consist of hepatocytes, and cholangiocytes, which are organized into epithelia that surround the lumina of bile duct–like structures. The organoids provide a potentially new model for liver regenerative processes, and were used to characterize the effect of different JAG1 mutations that cause: (a) Alagille syndrome (ALGS), a genetic disorder where NOTCH signaling pathway mutations impair bile duct formation, which has substantial variability in its associated clinical features; and (b) Tetralogy of Fallot (TOF), which is the most common form of a complex congenital heart disease, and is associated with several different heritable disorders. Our results demonstrate how an iPSC-based organoid system can be used with genome editing technologies to characterize the pathogenetic effect of human genetic disease-causing mutations.
Authors
Yuan Guan, Dan Xu, Phillip M. Garfin, Ursula Ehmer, Melissa Hurwitz, Greg Enns, Sara Michie, Manhong Wu, Ming Zheng, Toshihiko Nishimura, Julien Sage, Gary Peltz
Original citation JCI Insight. 2017;2(17):e94954. https://doi.org/10.1172/jci.insight.94954
Citation for this corrigendum: JCI Insight. 2023;8(20):e176034. https://doi.org/10.1172/jci.insight.176034
The authors recently became aware of an inadvertent error in Figure 7F. In the original version of Figure 7F, the representative ALGS1+/– bright-field image was incorrect and the same as the bright-field C1 panel presented in Figure 4K. The correct figure is shown below.
In addition, the y axes for the box plots shown in Figures 4K, 6F, and 7F were incorrectly labeled as Bile Acid Abundance. These axes instead should be labeled as HO2 number. The correct figures are shown below.
Finally, the figure legend for Supplemental Figure 1H has been updated to disclose that the day 9 CK19/HNF4A panel is the same as that presented in Figure 1C.
The HTML and PDF versions have been updated online.
The authors regret the errors.
