Inflammatory Monocytes Constrain YAP-Induced Cell Proliferation [scRNA-seq immune]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE329924 | GEO | 2026/07/01
REPOSITORIES: GEO
Similar Datasets
Project description:YAP and its paralog, TAZ are transcriptional co-activators of the Hippo pathway that regulate cell growth. Their structural distinctiveness suggests important independent functional differences. To investigate this further, we generated YAP- and TAZ-predominant clones in the liver and followed their long-term behavior. YAP clones rapidly de-differentiate cells into a stem cell-like state with inflammatory immune cell recruitment followed by their clearance. In contrast, TAZ clones promote an anti-inflammatory immune environment resulting in their long-term maintenance, massive organ growth and increased mortality. YAP clones recruit inflammatory blood-derived monocytes, which if inhibited permits YAP clonal growth. Consistent with these results, YAPHigh colorectal cancer (CRC) patients had a 67% 5-year survival rate, while TAZHigh CRC patients did not survive to 5 years. Similar trends were seen in hepatocellular carcinoma patients. These findings underscore the importance of understanding the intrinsic differences in YAP and TAZ biology as independent drivers of disease.
2026-07-01 | GSE314325 | GEO
Project description:YAP and its paralog, TAZ are transcriptional co-activators of the Hippo pathway that regulate cell growth. Their structural distinctiveness suggests important independent functional differences. To investigate this further, we generated YAP- and TAZ-predominant clones in the liver and followed their long-term behavior. YAP clones rapidly de-differentiate cells into a stem cell-like state with inflammatory immune cell recruitment followed by their clearance. In contrast, TAZ clones promote an anti-inflammatory immune environment resulting in their long-term maintenance, massive organ growth and increased mortality. YAP clones recruit inflammatory blood-derived monocytes, which if inhibited permits YAP clonal growth. Consistent with these results, YAPHigh colorectal cancer (CRC) patients had a 67% 5-year survival rate, while TAZHigh CRC patients did not survive to 5 years. Similar trends were seen in hepatocellular carcinoma patients. These findings underscore the importance of understanding the intrinsic differences in YAP and TAZ biology as independent drivers of disease.
2026-07-01 | GSE314318 | GEO
Project description:YAP and its paralog, TAZ are transcriptional co-activators of the Hippo pathway that regulate cell growth. Their structural distinctiveness suggests important independent functional differences. To investigate this further, we generated YAP- and TAZ-predominant clones in the liver and followed their long-term behavior. YAP clones rapidly de-differentiate cells into a stem cell-like state with inflammatory immune cell recruitment followed by their clearance. In contrast, TAZ clones promote an anti-inflammatory immune environment resulting in their long-term maintenance, massive organ growth and increased mortality. YAP clones recruit inflammatory blood-derived monocytes, which if inhibited permits YAP clonal growth. Consistent with these results, YAPHigh colorectal cancer (CRC) patients had a 67% 5-year survival rate, while TAZHigh CRC patients did not survive to 5 years. Similar trends were seen in hepatocellular carcinoma patients. These findings underscore the importance of understanding the intrinsic differences in YAP and TAZ biology as independent drivers of disease.
2026-07-01 | GSE314321 | GEO
Project description:In the acute phase of ischemic stroke, endothelial cell (EC) dysfunction leads to breakdown of the blood-brain barrier with increased vascular permeability, vascular inflammation, and transendothelial migration of leukocytes. ECs are also critical for long-term regenerative processes, such as post-stroke angiogenesis, enabling the transition from brain injury to repair. Yes-associated protein 1 (YAP) and WW domain-containing transcriptional regulator 1 (TAZ) are co-transcriptional regulators of EC proliferation and apoptosis. Several studies showed that YAP/TAZ is essential for developmental angiogenesis. However, the role of YAP/TAZ in adult angiogenesis and particularly in experimental stroke is unknown. Here, we subjected mice with an inducible EC-specific deletion of YAP and TAZ (YT-iKO) to 30-min middle cerebral artery occlusion (MCAo) followed by reperfusion to investigate the effects of endothelial YAP/TAZ on acute and long-term outcome after ischemic stroke. First, we examined mRNA expression of genes related to YAP/TAZ signaling in ischemic brain tissue, such as Id1, Smad6, Ankrd and Ccn2. We found a transient induction with highest expression levels acutely after stroke. Surprisingly, endothelial YAP/TAZ deficiency resulted in reduced lesion volumes 28 days after MCAo, whereas acute lesion size 3 days after stroke did not differ. Moreover, Yap/Taz iEC-KO animals showed no gross differences in vessels morphology 28 days after stroke, and no effect was detected on blood vessel density and EC density. We therefore speculated whether angiogenesis-independent effects of YAP/TAZ might also be associated with improved long-term outcome after stroke. To better understand the underlying mechanisms, we performed RNA sequencing of ECs isolated from ischemic brain tissue of YT-iKO compared with CTRL animals 72h post stroke. Here, we identified differently expressed gene sets involved in inflammatory responses. Therefore, we studied the non-endothelial tissue environment of the brain. We found, that EC YAP/TAZ deletion led to increased expression of anti-inflammatory genes accompanied by increased infiltration of myeloid cells, suggesting a protective phenotype. Besides, acute microglia proliferation was reduced in Y/T-iKO animals. Overall, our results provide new insights into the role of endothelial YAP/TAZ in neuroinflammation after cerebral ischemia. YAP/TAZ may therefore be a potential therapeutic target for the treatment of ischemic stroke.
2025-12-04 | GSE265949 | GEO
Project description:Uncontrolled Transforming growth factor-beta (TGFβ) signaling promotes aggressive metastatic properties in late-stage breast cancers. However, how TGFβ-mediated cues are directed to induce late-stage tumorigenic events is poorly understood, particularly given that TGFβ has clear tumor suppressing activity in other contexts. Here we demonstrate that the transcriptional regulators TAZ and YAP (TAZ/YAP), key effectors of the Hippo pathway, are necessary to promote and maintain TGFβ-induced tumorigenic phenotypes in breast cancer cells. Interactions between TAZ/YAP, TGFβ-activated SMAD2/3, and TEAD transcription factors reveal convergent roles for these factors in the nucleus. Genome-wide expression analyses indicate that TAZ/YAP, TEADs and TGFβ-induced signals coordinate a specific pro-tumorigenic transcriptional program. Importantly, genes cooperatively regulated by TAZ/YAP, TEAD, and TGFβ, such as the novel targets NEGR1 and UCA1, are necessary for maintaining tumorigenic activity in metastatic breast cancer cells. Nuclear TAZ/YAP also cooperate with TGFβ signaling to promote phenotypic and transcriptional changes in non-tumorigenic cells to overcome TGFβ repressive effects. Our work thus identifies crosstalk between nuclear TAZ/YAP and TGFβ signaling in breast cancer cells, revealing novel insight into late-stage disease-driving mechanisms. Expression profiling was conducted following the repression of the transcriptional regulators TAZ and YAP (TAZ/YAP), the TEAD family of transcription factors (TEAD1/2/3/4), or the TGFb signaling pathway (with SB-431542, an inhibitor of the TBRI recpeptor) in human MDA-MB-231-LM2 breast cancer cells treated with TGFβ1. Human MDA-MB-231-LM2-4 breast cancer cells were transfected with control siRNA, or siRNAs targeting TAZ/YAP or all four TEADs and were treated 24 hours later with 500pM TGFβ1 or 5mM SB-431542 for an additional 24 hours. Total RNA was isolated and twelve microarrays in total were performed, with each condition carried out three times on separate days. The Boston University Microarray Core generated the data using the Affymetrix Human Gene 1.0 St Array.
2014-04-02 | E-GEOD-56445 | biostudies-arrayexpress
Project description:Abstract Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via interaction with Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analysed Taz in vivo and ex vivo in comparison to Yap. Taz was expressed in activated satellite cells. siRNA knockdown or constitutive expression of wildtype or constitutively active TAZ mutants showed that TAZ promoted proliferation, a function that was shared with YAP. However, at later stages of myogenesis, TAZ also enhanced myogenic differentiation of myoblasts, whereas YAP inhibits such differentiation. Functionally, while muscle growth was mildly affected in Taz (gene symbol Wwtr1-/-) knockout mice, there were no overt effect on regeneration. However, conditional knockout of Yap in satellite cells of Pax7Cre-ERT2/+ : Yapflox/flox : Rosa26Lacz mice produced a marked regeneration deficit. To identify potential mechanisms, microarray analysis showed many common Taz/Yap targets, but Taz also regulates some genes independently of Yap, including myogenic genes such as Pax7, Myf5 and Myod1. Proteomic analysis of Yap/Taz revealed many common binding partners, but Taz also interacts with proteins distinct from Yap, that are mainly involved in myogenesis and aspects of cytoskeleton organization. Neither TAZ nor YAP bind members of the Wnt destruction complex but both extensively changed expression of Wnt and Wnt-cross talking genes with known roles in myogenesis. Finally, TAZ operates through Tead4 to enhance myogenic differentiation. In summary, Taz and Yap have overlapping functions in promoting myoblast proliferation but Taz then switches to promote myogenic differentiation.
2017-06-13 | PXD005751 | Pride
Project description:The Hippo pathway downstream effectors, Yap and Taz, play key roles in cell proliferation and tissue growth, regulating gene expression especially via interaction with Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analysed gene expression changes driven by Taz and compared these to Yap mediated changes to the transcriptome by measurement of gene expression on Affymetrix microarrays. To interrogate overlapping and unique transcriptional changes driven by these Hippo effectors, satellite cell-derived myoblasts were transduced with constitutively active TAZ S89A or YAP S127A retrovirus for 24h or 48h, with empty retrovirus as control. Triplicate microarray analyses of empty vector controls, hYAP1 S127A and TAZ S89A transgenic primary myoblasts were conducted.
2017-06-20 | E-MTAB-5395 | biostudies-arrayexpress
Project description:Angiogenesis, the process by which endothelial cells (ECs) form new blood vessels from existing ones, is intimately linked to the tissue's metabolic milieu and often occurs at nutrient-deficient sites. However, ECs rely on sufficient metabolic resources to support growth and proliferation. How endothelial nutrient acquisition and usage are regulated is unknown. Here we show that these processes are dictated by YAP/TAZ-TEAD – a transcriptional module whose function is highly responsive to changes in the tissue environment. ECs lacking YAP/TAZ or their transcriptional partners, TEAD1, 2, and 4 fail to divide, resulting in stunted vascular growth in mice. Conversely, activation of TAZ, the more abundant paralogue in ECs, boosts proliferation, leading to vascular hyperplasia. We find that YAP/TAZ promote angiogenesis by fueling nutrient mTORC1 signaling. By orchestrating the transcription of a repertoire of cell-surface transporters, YAP/TAZ-TEAD stimulate the import of amino acids and other essential nutrients, thereby enabling mTORC1 pathway activation. Dissociating mTORC1 from these nutrient inputs – elicited by the loss of Rag GTPases – inhibits mTORC1 activity and prevents YAP/TAZ-dependent vascular growth. These findings define a pivotal role for YAP/TAZ-TEAD in steering endothelial mTORC1 and illustrate the essentiality of coordinated nutrient fluxes in the vasculature.
2022-05-08 | PXD026872 | Pride
Project description:We characterized the epigenetic landscape of human colorectal cancer (CRC). To this extent, we performed gene expression profiling using high throughput sequencing (RNA-seq) and genome wide binding/occupancy profiling (ChIP-seq) for histone modifications correlated to transcriptional activity, enhancers, elongation and repression (H3K4me3, H3K4me1, H3K27Ac, H3K36me3, H3K27me3) in patient-derived organoids (PDOs), and in normal and tumoral primary colon tissues. We also generated ChIP-seq data for transcription factors YAP/TAZ in human CRC PDOs.
2021-02-23 | E-MTAB-8416 | biostudies-arrayexpress
Project description:We characterized the epigenetic landscape of human colorectal cancer (CRC). To this extent, we performed gene expression profiling using high throughput sequencing (RNA-seq) and genome wide binding/occupancy profiling (ChIP-seq) for histone modifications correlated to transcriptional activity, enhancers, elongation and repression (H3K4me3, H3K4me1, H3K27Ac, H3K36me3, H3K27me3) in patient-derived organoids (PDOs), and in normal and tumoral primary colon tissues. We also generated ChIP-seq data for transcription factors YAP/TAZ in human CRC PDOs.
2021-03-10 | E-MTAB-8448 | biostudies-arrayexpress