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Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE180528 | GEO | 2021/10/14

REPOSITORIES: GEO

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Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells.

Project description: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.

| S-EPMC8580886 | biostudies-literature

Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells [Hepatoblast RNA-seq]

Project description:Tbx3 regulates liver development in the mouse, but it's role in human liver development is unclear. We generated TBX3 knockout pluripotent stem cell lines and found that liver differentiation is also impaired in humans. Interestingly we noted expression of pancreas-specific genes during the liver differentiation in the TBX3 knockout line. To further investigate this phenomenon, we performed RNA-seq on cells at the hepatoblast stage of the liver differentiation. These studies demonstrated that the loss of TBX3 enhances pancreatic-gene signature, implicating TBX3 as a regulator of fate decisions.

2021-10-14 | GSE180526 | GEO

Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells [Pancreas RNA-seq]

Project description:Tbx3 regulates liver development in the mouse, but it's role in human liver development is unclear. We generated TBX3 knockout pluripotent stem cell lines and found that liver differentiation is also impaired in humans. Interestingly we noted expression of pancreas-specific genes during the liver differentiation in the TBX3 knockout line.To further investigate this phenomenon, we performed RNA-seq on cells from two stages of the pancreatic differentation. These studies demonstrated that the loss of TBX3 enhances pancreatic-gene signature, implicating TBX3 as a regulator of fate decisions.

2021-10-14 | GSE180525 | GEO

Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells [Hepatoblast ATAC-seq]

Project description:Tbx3 regulates liver development in the mouse, but it's role in human liver development is unclear. We generated TBX3 knockout pluripotent stem cell lines and found that liver differentiation is also impaired in humans. Interestingly we noted expression of pancreas-specific genes during the liver differentiation in the TBX3 knockout line. To further investigate this phenomenon, we performed ATAC-seq on cells at the hepatoblast stage of the liver differentiation. These studies demonstrated that the loss of TBX3 enhances pancreatic-gene signature, implicating TBX3 as a regulator of fate decisions.

2021-10-14 | GSE180527 | GEO

Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells

Project description:Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells

| PRJNA748588 | ENA

Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells [Hepatoblast RNA-seq]

Project description:Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells [Hepatoblast RNA-seq]

| PRJNA748592 | ENA

Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells [Hepatoblast ATAC-seq]

Project description:Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells [Hepatoblast ATAC-seq]

| PRJNA748593 | ENA

Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells [Pancreas RNA-seq]

Project description:Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells [Pancreas RNA-seq]

| PRJNA748594 | ENA

Zic3 enhances the generation of mouse induced pluripotent stem cells.

Project description:Zinc finger protein of the cerebellum (Zic)3, a member of Gli family of transcription factors (TFs), is essential for maintaining pluripotency of embryonic stem cells (ESCs) and has been reported to activate TF Nanog in an Oct4/Sox2-independent manner. Previously, we showed that Zic3 (Z), in combination with the Yamanka factors OCT4, SOX2, and KLF4 (OSK), induces neural progenitor-like cells from human fibroblasts. However, a similar combination of TFs (OSKZ) transduced in mouse embryonic fibroblasts resulted in enhanced induced pluripotent stem cells (iPSCs) formation compared with OSK alone, but not neuroprogenitors. OSKZ-derived iPSCs are indistinguishable from mESCs in colony morphology, expression of alkaline phosphatase and pluripotency genes, and embryoid body and teratoma formation. Zic3 activates the transcription of Nanog, a key pluripotency regulator, as evidenced by a luciferase promoter assay. During the course of iPSC derivation, Zic3-mediated enhanced expression of Nanog and Tbx3, gene known to enhance iPSCs derivation, is observed. Not only does Zic3 enhance the reprogramming efficiency, but also reactivation of the endogenous Zic3 protein is essential for the generation of iPSCs, as knockdown of Zic3 during the iPSC generation with OSKM significantly reduced the number of colonies. Together, our result uncovers an important role of Zic3 in generating mouse iPSCs.

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PDX1 Binding in human embryonic stem cell derived pancreatic progenitor cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-06-21 | E-GEOD-58686 | biostudies-arrayexpress