RNA-sequencing transcriptional profile of kidney capsule derived organ fibroblasts from adult mice, CRISPR-knockdown organ fibroblasts from adult mice, and human hearts
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE175765 | GEO | 2022/04/06
REPOSITORIES: GEO
Similar Datasets
Project description:RNA-sequencing transcriptional profile of kidney capsule derived organ fibroblasts from adult mice, CRISPR-knockdown organ fibroblasts from adult mice, and human hearts
| PRJNA733496 | ENA
Project description:Organ fibroblasts are essential components of homeostatic and diseased tissues, as they participate in sensing the microenvironment and communicating with other resident cells. They are also involved in pathological remodeling and fibrosis, caused by excessive deposition of connective tissue after injury, which impairs organ function. It is estimated that 45% of deaths in developed countries are linked to chronic fibrosis, yet current drugs on the market are both inefficient and non-specific to this condition. We have previously shown that cardiac fibroblasts display a unique cardiogenic identity, important for cardiac pathological remodeling. To determine whether fibroblasts from other organ systems display a molecular signature unique to their organ of origin, we characterized fibroblasts isolated from the adult mouse skin, lung, kidney, gonad and liver, and documented a molecular positional and organ signature that is likely a remnant from embryonic development. This information opens novel opportunities for the treatment of fibrotic diseases in a more precise, organ-specific manner.
2022-04-06 | GSE175762 | GEO
Project description:Organ fibroblasts are essential components of homeostatic and diseased tissues, as they participate in sensing the microenvironment and communicating with other resident cells. They are also involved in pathological remodeling and fibrosis, caused by excessive deposition of connective tissue after injury, which impairs organ function. It is estimated that 45% of deaths in developed countries are linked to chronic fibrosis, yet current drugs on the market are both inefficient and non-specific to this condition. We have previously shown that cardiac fibroblasts display a unique cardiogenic identity, important for cardiac pathological remodeling. To determine whether fibroblasts from other organ systems display a molecular signature unique to their organ of origin, we characterized fibroblasts isolated from the adult mouse skin, lung, kidney, gonad and liver, and documented a molecular positional and organ signature that is likely a remnant from embryonic development. This information opens novel opportunities for the treatment of fibrotic diseases in a more precise, organ-specific manner.
2022-04-06 | GSE175763 | GEO
Project description:RNA-sequencing transcriptional profile of CRISPR-knockdown organ fibroblasts from adult mice [CRISPR]
| PRJNA733498 | ENA
Project description:RNA-sequencing transcriptional profile of kidney capsule derived organ fibroblasts from adult mice [KidneyCapsule]
| PRJNA733497 | ENA
Project description:Organ fibroblasts are essential components of homeostatic and diseased tissues, as they participate in sensing the microenvironment and communicating with other resident cells. They are also involved in pathological remodeling and fibrosis, caused by excessive deposition of connective tissue after injury, which impairs organ function. It is estimated that 45% of deaths in developed countries are linked to chronic fibrosis, yet current drugs on the market are both inefficient and non-specific to this condition [1]. We have previously shown that cardiac fibroblasts display a unique cardiogenic identity, important for cardiac pathological remodeling. To determine whether fibroblasts from other organ systems display a molecular signature unique to their organ of origin, we characterized fibroblasts isolated from the adult mouse skin, lung, kidney, gonad and liver, and documented a molecular positional and organ signature that is likely a remnant from embryonic development. This information opens novel opportunities for the treatment of fibrotic diseases in a more precise, organ-specific manner.
2021-01-01 | GSE98783 | GEO
Project description:Kidney fibrosis presents a hallmark of chronic kidney disease. With ever-increasing patient numbers and limited treatment options available, novel strategies for therapeutic intervention in kidney disease are warranted. Fibrosis commonly results from a wound healing response to repeated or chronic tissue damage, irrespective of the underlying etiology, and can occur in virtually any solid organ or tissue. In order to identify targets relevant for kidney fibrosis, we aimed to employ CRISPR screening in primary human kidney fibroblasts. We demonstrate that CRISPR technology can be applied in primary kidney fibroblasts and can furthermore be used to conduct arrayed CRISPR screening using a high-content imaging readout in a whole genome-wide manner. Hits coming out of this screen were validated using orthogonal approaches and present starting points for validation of novel targets relevant to kidney disease.
| S-EPMC7309357 | biostudies-literature
Project description:Organ fibroblasts are essential components of homeostatic and diseased tissues. They participate in sculpting the extracellular matrix, sensing the microenvironment, and communicating with other resident cells. Recent studies have revealed transcriptomic heterogeneity among fibroblasts within and between organs. To dissect the basis of interorgan heterogeneity, we compare the gene expression of murine fibroblasts from different tissues (tail, skin, lung, liver, heart, kidney, and gonads) and show that they display distinct positional and organ-specific transcriptome signatures that reflect their embryonic origins. We demonstrate that expression of genes typically attributed to the surrounding parenchyma by fibroblasts is established in embryonic development and largely maintained in culture, bioengineered tissues and ectopic transplants. Targeted knockdown of key organ-specific transcription factors affects fibroblast functions, in particular genes involved in the modulation of fibrosis and inflammation. In conclusion, our data reveal that adult fibroblasts maintain an embryonic gene expression signature inherited from their organ of origin, thereby increasing our understanding of adult fibroblast heterogeneity. The knowledge of this tissue-specific gene signature may assist in targeting fibrotic diseases in a more precise, organ-specific manner.
| S-EPMC8959603 | biostudies-literature
Project description:Cardiac fibroblasts (CFs) are an attractive target for reducing pathological cardiac remodeling, and understanding the underlying mechanisms of these processes is the key to develop successful therapies for treating the pressure-overloaded heart. CF-specific knockout (KO) mouse lines with a Cre recombinase under the control of human TCF21 (hTCF21) promoter and/or an adeno-associated virus serotype 9 (AAV9)-hTCF21 system provide a powerful tool for understanding CF biology in vivo. Although a variety of rat disease models are vital for the research of cardiac fibrosis similar to mouse models, there are few rat models that employ cardiac cell-specific conditional gene modification, which has hindered the development and translational relevance of cardiac disease models. In addition, to date, there are no reports of gene manipulation specifically in rat CFs in vivo. Here, we report a simplified CF-specific rat transgenic model using an AAV9-hTCF21 system that achieved a CF-specific expression of transgene in adult rat hearts. Moreover, we successfully applied this approach to specifically manipulate mitochondrial morphology in quiescent CFs. In summary, this model will allow us to develop fast and simple rat CF-specific transgenic models for studying cardiovascular diseases in vivo.
| S-EPMC10972676 | biostudies-literature
Project description:The recent development and broad application of sequencing techniques at the single-cell level is generating an unprecedented amount of data. The different techniques have their individual limits, but the datasets also offer unexpected possibilities when utilized collectively. Here, we applied snRNA-seq in whole adult murine hearts from an inbred (C57BL/6NRj) and an outbred (Fzt:DU) mouse strain to directly compare the data with the publicly available scRNA-seq data of the tabula muris project. Explicitly choosing a single-nucleus approach allowed us to pin down the typical heart tissue-specific technical bias, coming up with novel insights on the mammalian heart cell composition. For our integrated dataset, cardiomyocytes, fibroblasts, and endothelial cells constituted the three main cell populations accounting for about 75% of all cells. However, their numbers severely differed between the individual datasets, with cardiomyocyte proportions ranging from about 9% in the tabula muris data to around 23% for our BL6 data, representing the prime example for cell capture technique related bias when using a conventional single-cell approach for these large cells. Most strikingly in our comparison was the discovery of a minor population of cardiomyocytes characterized by proliferation markers that could not be identified by analyzing the datasets individually. It is now widely accepted that the heart has an, albeit very restricted, regenerative potential. However there is still an ongoing debate where new cardiomyocytes arise from. Our findings support the idea that the renewal of the cardiomyocyte pool is driven by cytokinesis of resident cardiomyocytes rather than differentiation of progenitor cells. We thus provide data that can contribute to an understanding of heart cell regeneration, which is a prerequisite for future applications to enhance the process of heart repair.
| S-EPMC7291011 | biostudies-literature