Mus musculus
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ABSTRACT:
PROVIDER: PRJNA144579 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We set out to generate transcriptional maps of chondrocyte UPR gene networks in vivo using two mouse models (Schmid and Cog) of Schmid chondrodysplasia, in order to define the consequences of UPR activation for the adaptation, differentiation, and survival of chondrocytes experiencing ER stress during hypertrophy, thus providing insights into ER stress signaling and its impact on cartilage pathophysiology. Our data demonstrate that both models displayed similar unfolded protein responses (UPRs), involving activation of ER stress sensors Ire1 and Atf6 and upregulation of their downstream targets, including molecular chaperones, foldases, and ER-associated degradation machinery. Also upregulated were the emerging UPR regulators Wfs1 and Syvn1, recently identified UPR components including Armet and Creld2, and genes not previously implicated in ER stress such as Steap1 and Fgf21. Moreover, we transcriptionally profiled the expression of wildtype growth plate zone gene signatures in the mutant hypertrophic zones, in order to define the differentiation status of ER-stressed chondrocytes in the mutant hypertrophic zones. Hypertrophic zone gene upregulation and proliferative zone gene downregulation were both inhibited in Schmid hypertrophic zones, resulting in the persistence of a proliferative chondrocyte-like expression profile in ER-stressed Schmid chondrocytes. For the mutant hypertrophic zone gene expression profiling, the hypertrophic zone from one tibia from each of three two week old Schmid, wildtype (Schmid background), Cog, and wildtype (Cog background) mice was microdissected. In all cases, total RNA was extracted and amplified through two rounds of linear amplification, labelled with Cy3, and interrogated by microarray analysis using the Agilent 44K, mouse whole genome platform.
2012-01-01 | E-GEOD-30628 | biostudies-arrayexpress
Project description:We set out to generate transcriptional maps of chondrocyte UPR gene networks in vivo using two mouse models (Schmid and Cog) of Schmid chondrodysplasia, in order to define the consequences of UPR activation for the adaptation, differentiation, and survival of chondrocytes experiencing ER stress during hypertrophy, thus providing insights into ER stress signaling and its impact on cartilage pathophysiology. Our data demonstrate that both models displayed similar unfolded protein responses (UPRs), involving activation of ER stress sensors Ire1 and Atf6 and upregulation of their downstream targets, including molecular chaperones, foldases, and ER-associated degradation machinery. Also upregulated were the emerging UPR regulators Wfs1 and Syvn1, recently identified UPR components including Armet and Creld2, and genes not previously implicated in ER stress such as Steap1 and Fgf21. Moreover, we transcriptionally profiled the expression of wildtype growth plate zone gene signatures in the mutant hypertrophic zones, in order to define the differentiation status of ER-stressed chondrocytes in the mutant hypertrophic zones. Hypertrophic zone gene upregulation and proliferative zone gene downregulation were both inhibited in Schmid hypertrophic zones, resulting in the persistence of a proliferative chondrocyte-like expression profile in ER-stressed Schmid chondrocytes.
2012-01-01 | GSE30628 | GEO
Project description:We set out to determine the role of the IRE1/XBP1 pathway, the most ancient and highly conserved endoplasmic reticulum (ER) stress-sensing pathway of the unfolded protein response (UPR), in Schmid metaphyseal chondrodysplasia (MCDS). RNA derived from hypertrophic zones microdissected from growth plates of wildtype mice, mice lacking XBP1 activity in chondrocytes (Xbp1Cart?Ex2), mice carrying a COL10A1 pN617K mutation (ColXN617K), and compound mutants (C/X) was analyzed by whole genome microarray analysis. 1633 probes were differentially expressed between ColXN617K and wildtype, 215 probes were differentially expressed between Xbp1Cart?Ex2 and wildtype, and 1337 probes were differentially expressed between C/X and wildtype. 885 probes were differentially expressed between ColXN617K and wildtype but not Xbp1Cart?Ex2 and wildtype or C/X and wildtype, thus representing the XBP1-dependent response to hypertrophic chondrocyte ER stress. 688 probes were differentially expressed between ColXN617K and wildtype and between C/X and wildtype but not Xbp1Cart?Ex2 and wildtype, thus representing the XBP1-independent response to hypertrophic chondrocyte ER stress. Results were validated by qPCR. Entire growth plate hypertrophic zones were microdissected from one tibia from each of three 2-week old wildtype mice, three 2-week old mice carrying a COL10A1 p.N617K mutation (ColXN617K), three 2-week old mice lacking XBP1 activity in chondrocytes (Xbp1Cart?Ex2), and three 2-week old mice resulting from a cross between ColXN617K and Xbp1Cart?Ex2 (C/X).
2015-08-21 | E-GEOD-72261 | biostudies-arrayexpress
Project description:The human metaphyseal chondrodysplasia type Schmid is an autosomal dominant disorder associated with mutations in COL10A1 gene that result in ER retention of misfolded alpha(X) collagen in hypertrophic chondrocytes (HCs). In a MCDS transgenic mouse model (13del), we have previously implicated HC response and adaptation to ER stress as the underlying molecular pathogenesis of the disease. We generate microarray data from chondrocytes in WT, 13del and 13del:Chop-/- mice to elucidate the etiological role of ER stress signaling in MCDS.
2017-05-26 | GSE99306 | GEO
Project description:Emerging evidence implicates ER stress caused by unfolded mutant proteins in chondrocytes as the underlying pathology of chondrodysplasias. ER stress is triggered in hypertrophic chondrocytes (HCs) in a mouse model (13del) of metaphyseal chondrodysplasia type Schmid (MCDS) caused by misfolded mutant collagen X proteins, but the HCs do not undergo apoptosis, rather chondrocyte differentiation is altered causing skeletal abnormality. How 13del HCs can escape from apoptosis and survive ER stress is not understood. We compared using label-free quantitative mass spectrometry approach the proteomes of HCs isolated from 13del growth plates with normal HCs. In this paper we reveal significant changes in levels of proteins involved in in actin remodeling, glycolysis and ER-mitochondria communication in 13del HCs chondrocytes. Previous in vitro studies of chronic ER stress showed down-regulation of glycolysis and disrupted mitochondrial function leading to cell death. Our data showed that glucose uptake was maintained in ATDC5 chondrocytic cell lines expressing 13del collagen X. Furthermore expression of mitochondrial calcium channels was reduced while mitochondrial membrane polarity was maintained in in vivo 13del chondrocytes. Thus we propose that 13del HCs survive by a mechanism whereby changes in ER-mitochondria communication reduce import of calcium coupled with maintenance of mitochondrial membrane polarity.
2015-11-25 | PXD002125 | Pride
Project description:Axial growth of long bones occurs through a coordinated process of growth plate chondrocyte proliferation and differentiation. This maturation of chondrocytes is reflected in a zonal change in gene expression and cell morphology from resting to proliferative, prehypertrophic, and hypertrophic chondrocytes of the growth plate followed by ossification. A major experimental limitation in understanding growth plate biology and pathophysiology is the lack of a robust technique to isolate cells from the different zones, particularly from small animals. Here, we report on a new strategy for separating distinct chondrocyte populations from mouse growth plates. By transcriptome profiling of microdissected zones of growth plates, we identified novel, zone-specific cell surface markers and used these for flow cytometry and immunomagnetic cell separation to quantify, enrich, and characterize chondrocytes populations with respect to their differentiation status. This approach provides a novel platform to study cartilage development and characterize mouse growth plate chondrocytes to reveal unique cellular phenotypes of the distinct subpopulations within the growth plate.
2020-02-29 | GSE144362 | GEO
Project description:Longitudinal bone growth depends upon the execution of an intricate series of cellular activities by epiphyseal growth plate chondrocytes. In order to better understand these coordinated events, microarray analysis was used to compare gene expression in chondrocytes isolated from the proliferative and hypertrophic zones of the avian growth plate. In this experiment we compared pooled samples of proliferative and hypertrophic chondrocytes isolated from the chick growth plate. The expression of 745 genes was found to differ 3-fold or greater at the 0.05 level of probability.
2009-10-16 | GSE18568 | GEO
Project description:In order to better understand chondrodysplasia disease mechanisms, we induced hypertrophic chondrocytes from chondrodysplasia-specific iPSCs and analyzed their gene expression profile. This dataset includes the expression data obtained from iPSC-derived cartilage pellets on day 56 of hypertrophic induction. Three COL10A1 mutants and two MATN3 mutants were compared to their isogenic controls to determine the effects of each mutation on the unfolded protein response.
2020-05-20 | GSE148728 | GEO
Project description:Longitudinal bone growth depends upon the execution of an intricate series of cellular activities by epiphyseal growth plate chondrocytes. In order to better understand these coordinated events, microarray analysis was used to compare gene expression in chondrocytes isolated from the proliferative and hypertrophic zones of the avian growth plate. In this experiment we compared pooled samples of proliferative and hypertrophic chondrocytes isolated from the chick growth plate. The expression of 745 genes was found to differ 3-fold or greater at the 0.05 level of probability. Experiment Overall Design: We examined 8 samples using arrays: 4 from proliferative and 4 from hypertrophic chondrocytes.
2009-10-23 | E-GEOD-18568 | biostudies-arrayexpress
Project description:Here we show a multifunctional protein, Hnrnpk, is essential for preventing excessive apoptosis and premature differentiation of growth plate chondrocytes. These datas were the RNA-seq of E18.5 growth plate chondrocytes with or without Hnrnpk.
2022-09-28 | GSE197283 | GEO