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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE180525 | GEO | 2021/10/14

REPOSITORIES: GEO

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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 [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

Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis

Project description:MAPK pathway-driven tumorigenesis, often induced by BRAFV600E, relies on epithelial dedifferentiation. However, how lineage differentiation events are reprogrammed remains unexplored. Here, we demonstrate that proteostatic reactivation of developmental factor, TBX3, accounts for BRAF/MAPK-mediated dedifferentiation and tumorigenesis. During embryonic development, BRAF/MAPK upregulates USP15 to stabilize TBX3, which orchestrates organogenesis by restraining differentiation. The USP15-TBX3 axis is reactivated during tumorigenesis, and Usp15 knockout prohibits BRAFV600E-driven tumor development in a Tbx3-dependent manner. Deleting Tbx3 or Usp15 leads to tumor redifferentiation, which parallels their overdifferentiation tendency during development, exemplified by disrupted thyroid folliculogenesis and elevated differentiation factors such as Tpo, Nis, Tg. The clinical relevance is highlighted in that both USP15 and TBX3 highly correlates with BRAFV600E signature and poor tumor prognosis. Thus, USP15 stabilized TBX3 represents a critical proteostatic mechanism downstream of BRAF/MAPK-directed developmental homeostasis and pathological transformation, supporting that tumorigenesis largely relies on epithelial dedifferentiation achieved via embryonic regulatory program reinitiation.

2024-02-19 | PXD049704 |

Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis.

2024-04-15 | GSE255930 | GEO

Tbx3 controls Dppa3 levels to regulate exit from pluripotency towards mesodermal lineage

Project description:Tbx3, a member of the T-box family, plays important roles in development, stem cells, nuclear reprogramming and cancer. Loss of Tbx3 induces differentiation in mouse embryonic stem cells (mESCs). However, we show that mESCs exist in an alternate stable pluripotent state in the absence of Tbx3. In-depth transcriptome analysis of this mESC state reveals Dppa3 as a direct downstream target of Tbx3. Also Tbx3 facilitates the cell fate transition from pluripotent cells to mesoderm progenitors by directly repressing Wnt pathway members required for differentiation. Wnt signaling regulates differentiation of mESCs into mesoderm progenitors and helps maintain a naïve pluripotent state. We show that Tbx3, a downstream target of Wnt signaling, fine-tunes these divergent roles of Wnt signaling in mESCs. In conclusion, we identify a signaling-TF axis that controls the exit of mESCs from a self-renewing pluripotent state towards mesoderm differentiation. ChIPSeq and RNASeq (population and single cell) was performed on the indicated cell lines. Replicates are indicated as needed. The mm9 genome assembly was used. For single cell mRNA-Seq preparation, SSEA1+DAPI- mESCs were sorted and collected.

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TBX3 defines the functional identity of hypothalamic melanocortin neurons

Project description:Purpose: Identify cellular pathways controlled by Tbx3 Methods: RNA sequencing of hypothalamic primary neurons from Tbx3 loxP/loxP mice infected with Ad-Cre or Ad-GFP viruses. Results: Unbiased pathway analysis revealed that Tbx3 deletion in primary neurons significantly affected the expression of genes involved in several pathways responsible for controlling cellular proliferation, differentiation and determination of cellular fate. Conclusions: Tbx3 in primary neurons might be implicated in the development and maintenance of neuronal identity.

2019-01-22 | GSE119883 | GEO

Tbx3 controls Dppa3 levels to regulate exit from pluripotency towards mesodermal lineage

2015-07-21 | GSE60066 | GEO

A dynamic role of Tbx3 in the pluripotency circuitry

Project description:Pluripotency represents a cell state comprising a fine-tuned pattern of transcription factor activity required for embryonic stem cell (ESC) self-renewal. TBX3 is the earliest expressed member of the T-box transcription factor family and is involved in maintenance and induction of pluripotency. Hence, TBX3 is believed to be a key member of the pluripotency circuitry, with loss of TBX3 coinciding with loss of pluripotency. We report a dynamic expression of TBX3 in vitro and in vivo using genetic reporter tools tracking TBX3 expression in mouse ESCs (mESCs). Low TBX3 levels are associated with reduced pluripotency, resembling the more mature epiblast. Notably, TBX3-low cells maintain the intrinsic capability to switch to a TBX3-high state and vice versa. Additionally, we show TBX3 to be dispensable for induction and maintenance of naive pluripotency as well as for germ cell development. These data highlight novel facets of TBX3 action in mESCs.

2015-12-09 | GSE73862 | GEO

A dynamic role of Tbx3 in the pluripotency circuitry

2015-12-09 | E-GEOD-73862 | biostudies-arrayexpress

Mouse embryo heart, e10.5 AVC: Control vs. Tbx3 hypomorphic mutant

Project description:Transcriptional profiling of the atrioventricular canal from e10.5 mouse hearts comparing wild-type control with Tbx3 GH/N hypomorphic mutant microdissected tissue. The goal was to identify direct and indirect targets of the transcription factor Tbx3, because Tbx3 is expressed in the AVC and hypomorphs develop embryonic AV conduction block at e12.5. Two-condition experiment, wild-type control and Tbx3 mutant AVC tissue. Tissue from 5 hearts was pooled to make each sample. Biological replicates: 4.

2011-04-01 | E-GEOD-24122 | biostudies-arrayexpress

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