Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Loss of Mst1/2 activity promotes non-mitotic hair cell generation in the neonatal organ of Corti

ABSTRACT: We used in vitro RNA-sequencing to show that the Hippo signaling pathway is involved in HC damage and self-repair processes. Turning off Hippo signaling through Mst1/2 inhibition or Yap overexpression induces YAP nuclear accumulation, especially in supporting cells, which induces supernumerary HC production and HC regeneration after injury. Mechanistically, these effects of Hippo signaling work synergistically with the Notch pathway.

ORGANISM(S): Mus musculus

PROVIDER: GSE213784 | GEO | 2022/09/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

PAX3-FOXO1 suppresses cellular senescence through RASSF4-mediated restraint of the mammalian Hippo/MST1 pathway

Project description:Alveolar rhabdomyosarcoma (aRMS) is an aggressive sarcoma of skeletal muscle characterized by expression of the PAX3-FOXO1 fusion gene. Despite its discovery over almost 20 years ago, PAX3-FOXO1 remains an enigmatic tumor driver. Previously, we reported that PAX3-FOXO1 supports aRMS initiation by enabling bypass of cellular senescence. Here, we show that bypass occurs in part by PAX3-FOXO1-mediated upregulation of RASSF4, a Ras-association domain family (RASSF) member, which then suppresses the evolutionarily conserved mammalian Hippo/Mst1 pathway. RASSF4 loss-of-function activates Hippo/Mst1 and inhibits downstream YAP, causing aRMS cell cycle arrest and senescence. This is the first evidence for an oncogenic role for RASSF4, and a novel mechanism for Hippo signaling suppression in human cancer. Human skeletal muscle myoblasts (HSMMs) were retrovirally transduced with either an empty vector (Vp, pK1) or PAX3-FOXO1 (PFp, pK1-PAX3-FOXO1) and selected on puromycin. Presenescent (presen) cells were harvested before the senescence checkpoint. Since cells expressing PAX3-FOXO1 can bypass the senescence checkpoint, postsenescent (postsen) cells expressing PAX3-FOXO1 were also harvested. the gene expression affected by the introduction of PAX3-FOXO1

2014-05-15 | E-GEOD-40543 | biostudies-arrayexpress

RNA sequencing data from wild type and Mst1/2 knockout esophageal epithelium

Project description:Hippo signaling regulates the homeostasis of multiple organs. Mst1 and Mst2 (Mst1/2) are critical components of the Hippo signaling pathway. Here, we utilized RNA sequencing to determine the transcriptional change in the esophageal epithelium upon Mst1/2 deletion. The analysis of gene expression profiles allows us to understand the role of Mst1/2 in the regulation of various biological processes in the esophageal epithelium.

2024-02-26 | GSE248501 | GEO

Gene expression profiling of effect of Yap inhibition in a genetically engineered mouse model of hepatocellular carcinoma

Project description:Defective Hippo/YAP signaling in the liver results in tissue overgrowth and development of hepatocellular carcinoma (HCC). Here, we uncover mechanisms of YAP-mediated hepatocyte reprogramming and HCC pathogenesis. We show that YAP functions as a rheostat maintaining metabolic specialization, differentiation and quiescence within the hepatocyte compartment. Importantly, treatment with siRNA-lipid nanoparticles (siRNA-LNPs) targeting YAP restores hepatocyte differentiation and causes pronounced tumor regression in a genetically engineered mouse HCC model (mice with liver-specific Mst1/Mst2 double knockout). Furthermore, YAP targets are enriched in an aggressive human HCC subtype characterized by a proliferative signature and absence of CTNNB1 mutations. Thus, our work reveals Hippo signaling as a key regulator of positional identity of hepatocytes, supports targeting YAP using siRNA-LNPs as a paradigm of differentiation-based therapy, and identifies an HCC subtype potentially responsive to this approach. Mice with liver-specific Mst1/Mst2 double-knockout (Adeno-Cre injected Mst1-/-; Mst2Flox/Flox mice) were monitored for the formation of HCC by ultrasound imaging. Animals were then randomized to be treated by intravenous injection of either siYap-LNPs or siLuciferase-LNPs for a period of 9 days.

2015-03-07 | E-GEOD-65665 | biostudies-arrayexpress

Microarray of Mst1/2 deleted epithelial cells from E18.5 mouse lungs

Project description:ShhCre;Mst1/2flx/flx (Mst1/2 D/D) mice were generated to conditionally delete Mst1 and Mst2 from epithelial progenitors during lung morphogenesis. Lungs from E18.5 control and Mst1/2 D/D mice were mechanically and enzymatically dissociated to generate single cell suspension. Epcam(+) cells were isolated using magnetic microbeads. Microarray analysis of mRNAs isolated from Epcam(+) epithelial cells from E18.5 control and Mst1/2 D/D mice was performed to identify transcriptional changes following deletion of the mammalian Hippo kinases (Mst1 and Mst2) from the embryonic lung. The mammalian Hippo kinases, Mst1 and Mst2, were conditionally deleted in epithelial progenitors of the developing lung using ShhCre. Epcam(+) epithelial cells were isolated from the lungs of E18.5 control and Mst1/2 deleted mice. mRNA isolated from Epcam(+) epithelial cells was analyzed by microarray.

2015-01-01 | E-GEOD-61582 | biostudies-arrayexpress

Gene expression profile of mouse liver cancer (Sav1 and Mst1/2 Knockout models)

Project description:Hippo pathway is evolutionarily well conserved. All core components of the pathway identified to date have one or more mammalian orthologs, including MST1/2 (Hippo), SAV1 (Salvador, also known as WW45), LATS1/2 (Warts), MOB1 (Mats), YAP1 and its paralog WWTR1 (also known as TAZ) (Yorkie), and TEAD1/2/3/4 (Scalloped). Ectopic over-expression of YAP1 in mouse liver led to develop hepatocellular carcinoma (HCC). HCC is the third most common cause of cancer-related death in the world, and accounts for an estimated 600,000 deaths annually. Lack of molecular classification and clinical heterogeneity of this malignant disease hampered the development of standardized treatment. To investigate roles of Hippo pathway in liver carcinogenesis, we generated liver-specific Mst1/2 -/- and Sav1 -/- mouse models and collected gene expression data from them. Our study provided new understanding on molecular characteristics of HCC. Sav1 and Mst1/2 Knockout models

2014-08-23 | E-GEOD-32510 | biostudies-arrayexpress

PAX3-FOXO1 suppresses cellular senescence through RASSF4-mediated restraint of the mammalian Hippo/MST1 pathway

2014-05-15 | GSE40543 | GEO

Transcription profiles of WT or MST1/2-KO total, CD8+ and CD8- DCs in vivo

Project description:CD8+ DCs play key role in CD8+ T cell priming, however, the underlying signaling mechansim is unclear. We used a data-driven network-based systems biology approach and identified Hippo signaling kinases as key selective modualtors in CD8+ DCs. We focused on Mst1/Stk4 to further investigate the novel function of Hippo signaling in CD8+ DCs. All transcriptional profies were evalated by microarray. 1) We used microarrays of total DCs in previous (GSE98481) and current studies to reverse engineer a DC-specific signaling interactome (DCI). 2) We integrated DCI with profiles of sorted CD8+ with CD8- DCs to identify signaling drivers of CD8+ DCs. 3) We profiled and compared Mst1/2-KO with WT cells from total, CD8+ and CD8- DCs to understand the mechanism of Mst1 in CD8+ DCs.

2018-06-08 | GSE100772 | GEO

Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type, Mst1/2 dKO and Mst1/2; Yap tKO Initial segments of Epididymis Transcriptomes

Project description:mRNA profiles of 4 week-old contol and Mst1/2 dKO and Mst1/2; Yap tKO Initial segments of Epididymis were generated by deep sequencing, in triplicate, using Illumina HiSeq platform.

2020-04-29 | GSE138519 | GEO

Regenerative reprogramming of the intestinal stem cell state via Hippo signaling suppresses metastatic colorectal cancer [DSS_scRNAseq]

Project description:Although the Hippo transcriptional coactivator YAP is considered oncogenic in many tissues, its roles in intestinal homeostasis and colorectal cancer (CRC) remain controversial. Here, we demonstrate that the Hippo kinases LATS1/2 and MST1/2, which inhibit YAP activity, are required for maintaining Wnt signaling and canonical stem cell function. Hippo inhibition induces a distinct epithelial cell state marked by low Wnt signaling, a wound-healing response, and transcription factor Klf6 expression. Notably, loss of LATS1/2 or overexpression of YAP is sufficient to reprogram Lgr5+ cancer stem cells to this state and thereby suppress tumor growth in organoids, patient-derived xenografts, and mouse models of primary and metastatic CRC. Finally, we demonstrate that genetic deletion of YAP and its paralog TAZ promotes the growth of these tumors. Collectively, our results establish the role of YAP as a tumor suppressor in the adult colon and implicate Hippo kinases as therapeutic vulnerabilities in colorectal malignancies.

2020-06-24 | GSE152369 | GEO

Regenerative reprogramming of the intestinal stem cell state via Hippo signaling suppresses metastatic colorectal cancer [Organoid_RNAseq]

2020-06-24 | GSE152374 | GEO