Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells
Summary
Tbx3 has been identified as a regulator of liver development in the mouse, but its function in human liver development remains unknown. TBX3 mutant human pluripotent stem cell (PSC) lines were generated using CRISPR/Cas9 genome editing. TBX3 loss led to impaired liver differentiation and an upregulation of pancreatic gene expression, including PDX1, during a hepatocyte differentiation protocol. Other pancreatic genes, including NEUROG3 and NKX2.2, displayed more open chromatin in the TBX3 mutant hepatoblasts. Using a pancreatic differentiation protocol, cells lacking TBX3 generated more pancreatic progenitors and had an enhanced pancreatic gene expression signature at the expense of hepatic gene expression. These data highlight a potential role of TBX3 in regulating hepatic and pancreatic domains during foregut patterning, with implications for enhancing the generation of pancreatic progenitors from PSCs. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
| Authors | Mukherjee S, French DL, Gadue P |
|---|---|
| Journal | Stem cell reports |
| Publication Date | 2021 Nov 9;16(11):2617-2627 |
| PubMed | 34653400 |
| PubMed Central | PMC8580886 |
| DOI | 10.1016/j.stemcr.2021.09.004 |