Similar Datasets
Project description:Transcription Factor RFX3 Stabilizes Mammary Basal Cell Identity
| PRJNA790932 | ENA
Project description:Understanding the mechanisms that specify neuronal subtypes is important to unravel the complex mechanisms of neuronal circuit assembly. Here we have identified a novel role for the transcription factor AP2γ in progenitor and neuronal subtype specification in the cerebral cortex. Conditional deletion of AP2γ causes misspecification of basal progenitors starting at mid-neurogenesis and gain-of-function experiments show that AP2γ directly regulates the expression of several genes characteristic for basal progenitors, such as Math3 and Tbr2. The misspecification of basal progenitors upon loss of AP2γ resulted in their increased death and the ultimate reduction of callosal layer II/III projection neurons. This had pronounced effects on visual performance with a strong reduction of visual acuity. Thus, we have identified a novel regulator of basal progenitor fate regulating the number of layer II/III neurons in an area-specific manner and revealing their importance for accurate function of the visual cortex.
2009-09-22 | GSE12134 | GEO
Project description:During development cells become gradually restricted in their differentiation potential by the repression of alternative cell fates. While we know that the Polycomb complex plays a crucial role in this process, it still remains unclear how alternative fate genes are specifically targeted for silencing in different cell lineages. We address this question by studying Ultrabithorax (Ubx), a multi-lineage transcription factor (TF) of the Hox class, in the mesodermal and neuronal lineages using sorted nuclei of Drosophila embryos and by interfering with Ubx in mesodermal cells that have already initiated differentiation. We find that Ubx is a key regulator of lineage development, as its mesoderm-specific depletion leads to the de-repression of many genes normally expressed in other lineages. Ubx silences expression of alternative fate genes by interacting with and retaining the Polycomb Group (PcG) protein Pleiohomeotic (Pho) at Ubx targeted genomic regions, thereby setting repressive chromatin marks in a lineage-dependent manner. In sum, our study demonstrates that Ubx stabilizes lineage choice by suppressing the multi-potency encoded in the genome in a lineage-specific manner via its interaction with Pho. This mechanism may explain why the Hox code is maintained throughout the lifecycle, since it seems to set a block to transdifferentiation in many adult cells.
2019-05-04 | GSE121670 | GEO
Project description:During development cells become gradually restricted in their differentiation potential by the repression of alternative cell fates. While we know that the Polycomb complex plays a crucial role in this process, it still remains unclear how alternative fate genes are specifically targeted for silencing in different cell lineages. We address this question by studying Ultrabithorax (Ubx), a multi-lineage transcription factor (TF) of the Hox class, in the mesodermal and neuronal lineages using sorted nuclei of Drosophila embryos and by interfering with Ubx in mesodermal cells that have already initiated differentiation. We find that Ubx is a key regulator of lineage development, as its mesoderm-specific depletion leads to the de-repression of many genes normally expressed in other lineages. Ubx silences expression of alternative fate genes by interacting with and retaining the Polycomb Group (PcG) protein Pleiohomeotic (Pho) at Ubx targeted genomic regions, thereby setting repressive chromatin marks in a lineage-dependent manner. In sum, our study demonstrates that Ubx stabilizes lineage choice by suppressing the multi-potency encoded in the genome in a lineage-specific manner via its interaction with Pho. This mechanism may explain why the Hox code is maintained throughout the lifecycle, since it seems to set a block to transdifferentiation in many adult cells.
2019-05-02 | GSE121752 | GEO
Project description:Mammary gland development is fueled by stem cell self-renewal and differentiation. External cues from the microenvironment coupled with internal cues such as post-transcriptional regulation exerted by microRNAs regulate stem cell behavior and fate. Here, we have identified a miR-205 regulatory network required for mammary gland ductal development and stem cell regeneration following transplantation into the cleared mammary fat pad. In the postnatal mammary gland, miR-205 is predominantly expressed in the basal/stem cell enriched population. Conditional deletion of miR-205 in mammary epithelial cells impairs stem cell self-renewal and mammary regenerative potential in the in vitro mammosphere formation assay and in vivo mammary reconstitution. miR-205 null transplants display significant changes in basal cells, basement membrane, and stroma. NKD1 and PTPA, which inhibit the Wnt signaling pathway, and AMOT, which causes YAP cytoplasmic retention and inactivation were identified as miR-205 downstream mediators. These studies also confirmed that miR-205 is a direct ?Np63 target gene that is critical for the regulation of basal cell identity. Stem Cells 2018;36:1875-15.
| S-EPMC6379077 | biostudies-literature
Project description:Basal breast cancers, an aggressive breast cancer subtype that has poor treatment options, are thought to arise from luminal mammary epithelial cells that undergo basal-like plasticity through poorly understood mechanisms. Using genetic mouse models and ex vivo primary organoid cultures, we show that conditional co-deletion of the LATS1 and LATS2 kinases, key effectors of Hippo pathway signaling, in mature mammary luminal epithelial cells promotes the development of basal-like carcinomas that metastasize over time. Genetic co-deletion experiments revealed that phenotypes resulting from the loss of LATS1/2 activity are dependent on the transcriptional regulators YAP/TAZ. Notably, transcriptional analyses of LATS1/2-deleted mammary epithelial cells revealed a gene expression program that associates with human basal breast cancers. Our study demonstrates in vivo roles for the LATS1/2 kinases in mammary epithelial homeostasis and luminal-basal fate control and implicates signaling networks induced upon the loss of LATS1/2 activity in the development of basal breast cancers.
2022-09-26 | GSE196555 | GEO
Project description:Large heteromeric multiprotein complexes play pivotal roles at every step of gene expression in eukaryotic cells. Among them, the 20-subunits basal transcription factor TFIID nucleates RNA polymerase II preinitiation complex at gene promoters. Here, by combining systematic RNA-immunoprecipitation experiments, single-molecule imaging, proteomics and structure-function analyses, we show that TFIID is built using co-translational assembly. We discovered that all early steps of TFIID assembly, involving protein heterodimerization, happen during protein synthesis. Strikingly, we identify TAF1 – the largest protein in the complex – as a flexible scaffold subunit that co-translationally recruits preassembled TFIID submodules found populating the cytoplasm of cells. Consequently, TAF1 depletion leads to a cytoplasmic accumulation of TFIID building blocks. Altogether, our data suggest a multistep hierarchical model for TFIID biogenesis that culminates with the co-translational assembly on nascent TAF1 polypeptide, that works as a ‘driver’ subunit. We envision that this assembly strategy could be shared with other large heteromeric protein complexes.
2023-07-04 | PXD036358 | Pride
Project description:To investigate the effect of macrophages on mammary basal cells, we established a macrophage depletion mouse model by clodronate liposome (CL) intraperitoneal injection, and the mammary basal cells were collected by FACS sorting. We then performed RNA-seq analysis on clodronate liposome (CL) treated mammary basal cells compared to control.
2023-04-20 | GSE210268 | GEO
Project description:The epiblast is the first cell type that forms apical-basal polarity de novo as the mouse embryo implants into the maternal uterus, while the extraembryonic neighbours of the epiblast - trophectoderm and primitive endoderm - retain their pre-established polarity beyond implantation [1]; however, it is still unclear how the epiblast establishes apical-basal polarity de novo. Here, we focused on Rap1 signaling pathway, which is activated during the transition of the epiblast from the naïve to primed state of pluripotency during implantation [2]. Through the preestablished in vitro three-dimensional culture system [3], genetic knockouts and proximity-biotinylation analyses, we found that Rap1 integrates multiple signals that contribute to de novo formation of apical-basal polarity. Importantly, formation of apical-basal polarity in the epiblast is essential for its correct patterning and proper communication with the extraembryonic lineages. Altogether, these results not only dissect molecular details of de novo apical-basal polarity formation, but also have broader implications for epithelial polarity and development.
2022-06-14 | PXD028315 | Pride
Project description:The mechanisms regulating breast cancer differentiation state are poorly understood. Of particular interest are molecular regulators controlling the highly aggressive and poorly differentiated traits of basal-like breast carcinomas. Here we show that the Polycomb factor EZH2 maintains the differentiation state of basal-like breast cancer cells, and promotes the expression of progenitor-associated and basal-lineage genes. Specifically, EZH2 regulates the composition of basal-like breast cancer cell populations by promoting a M-bM-^@M-^\bi-lineageM-bM-^@M-^] differentiation state, in which cells co-express basal- and luminal-lineage markers. We show that human basal-like breast cancers contain a subpopulation of bi-lineage cells, and that EZH2-deficient cells give rise to tumors with a decreased proportion of such cells. Bi-lineage cells express genes that are active in normal luminal progenitors, and possess increased colony formation capacity, consistent with a primitive differentiation state. We found that GATA3, a driver of luminal differentiation, performs a function opposite to EZH2, acting to suppress bi-lineage identity and luminal progenitor gene expression. GATA3 levels increase upon EZH2 silencing, leading to the observed decrease in bi-lineage cell numbers. Our findings reveal a novel role for EZH2 in controlling basal-like breast cancer differentiation state and intra-tumoral cell composition. Total of four treatments (HCC70 cells stably expressing shEZH2, shEED, or EZH2 cDNA, and MDA-MB-468 cells stably expressing shEZH2) were done in duplicates, each with its own control.
2012-09-21 | E-GEOD-36939 | biostudies-arrayexpress