ScRNA-seq Analysis of Dmp1cre-DTAki/wt and wt skin
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE305068 | GEO | 2025/08/15
REPOSITORIES: GEO
Similar Datasets
Project description:Using oligomycin A-treated MLO-Y4 cells and primary murine aging osteocytes as a model of cells with mitochondrial dysfunction, it is demonstrated that when mitochondria are damaged, osteocytes tend to release signaling compounds including adenosine diphosphate. We identified that the nucleotide membrane receptors P2Y2 and P2Y6 transduced the ADP signal to Mfn2, a critical regulator of osteocyte mitochondrial transfer. Whole RNA sequencing (RNA-seq) analysis of mouse cortical bone showed that mitochondrial metabolism is impaired in aged osteocytes, and there are more extracellular nucleotides released into the matrix in cortical bone in aged mice as compared to that in young mice. Aging decreases expression levels of P2Y2/P2Y6 and Mfn2.
2024-01-24 | GSE235103 | GEO
Project description:Aging is associated with osteoporosis and remodeling of bone marrow microenvironment, skewing hematopoiesis. Obesity may accelerate aging process. We use bulk-RNA sequencing to measure the transcriptomic changes of bone cells caused by long-term HFD feeding in aged mice, which mainly includes osteocytes and other bone marrow stromal cells.
2023-11-15 | GSE218105 | GEO
Project description:Some cuboidal osteoblasts differentiate into bone-embedded, dendrite-bearing osteocytes through the poorly-understood process of osteocytogenesis. Here, we report that the transcription factor Sp7 plays an essential role in osteocytogenesis. Severe defects in bone integrity and osteocyte dendrite morphology are noted in mice lacking Sp7 at the stage of the osteoblast-to-osteocyte transition. In osteocytes, Sp7 controls expression of a neuronally-enriched gene network. Analysis of the osteocyte-specific Sp7 cistrome reveals distinct genomic binding motifs and target sites distinct from those in osteoblasts. Amongst osteocyte-specific Sp7 targets, the secreted peptide osteocrin rescues Sp7-deficient defects. Single-cell transcriptional profiling of cells undergoing osteocytogenesis identifies novel Sp7-dependent transitional cell types enriched in genes linked to human fracture risk. Finally, humans with an SP7 R316C mutation display osteocyte morphology defects similar to those observed in mouse models. These findings demonstrate that cuboidal osteoblasts use a neuronally-enriched Sp7/osteocrin gene expression program to differentiate into dendrite-bearing osteocytes.
2021-09-20 | GSE154718 | GEO
Project description:Some cuboidal osteoblasts differentiate into bone-embedded, dendrite-bearing osteocytes through the poorly-understood process of osteocytogenesis. Here, we report that the transcription factor Sp7 plays an essential role in osteocytogenesis. Severe defects in bone integrity and osteocyte dendrite morphology are noted in mice lacking Sp7 at the stage of the osteoblast-to-osteocyte transition. In osteocytes, Sp7 controls expression of a neuronally-enriched gene network. Analysis of the osteocyte-specific Sp7 cistrome reveals distinct genomic binding motifs and target sites distinct from those in osteoblasts. Amongst osteocyte-specific Sp7 targets, the secreted peptide osteocrin rescues Sp7-deficient defects. Single-cell transcriptional profiling of cells undergoing osteocytogenesis identifies novel Sp7-dependent transitional cell types enriched in genes linked to human fracture risk. Finally, humans with an SP7 R316C mutation display osteocyte morphology defects similar to those observed in mouse models. These findings demonstrate that cuboidal osteoblasts use a neuronally-enriched Sp7/osteocrin gene expression program to differentiate into dendrite-bearing osteocytes.
2021-09-20 | GSE154717 | GEO
Project description:Some cuboidal osteoblasts differentiate into bone-embedded, dendrite-bearing osteocytes through the poorly-understood process of osteocytogenesis. Here, we report that the transcription factor Sp7 plays an essential role in osteocytogenesis. Severe defects in bone integrity and osteocyte dendrite morphology are noted in mice lacking Sp7 at the stage of the osteoblast-to-osteocyte transition. In osteocytes, Sp7 controls expression of a neuronally-enriched gene network. Analysis of the osteocyte-specific Sp7 cistrome reveals distinct genomic binding motifs and target sites distinct from those in osteoblasts. Amongst osteocyte-specific Sp7 targets, the secreted peptide osteocrin rescues Sp7-deficient defects. Single-cell transcriptional profiling of cells undergoing osteocytogenesis identifies novel Sp7-dependent transitional cell types enriched in genes linked to human fracture risk. Finally, humans with an SP7 R316C mutation display osteocyte morphology defects similar to those observed in mouse models. These findings demonstrate that cuboidal osteoblasts use a neuronally-enriched Sp7/osteocrin gene expression program to differentiate into dendrite-bearing osteocytes.
2021-09-20 | GSE154716 | GEO
Project description:Estrogens are well known steroid hormones necessary to maintain bone health. In addition, mechanical loading, which estrogen signaling may intersect with the Wnt/β-catenin pathway, is also essential for bone health. As osteocytes are known as the major mechanosensory cells embedded in mineralized bone matrix, osteocyte ERα deletion mice (ERαÎOcy/ÎOcy) were generated by mating ERα floxed mice with Dmp1-Cre mice to determine functions of ERα in osteocytes. Trabecular bone mineral density of female, but not male ERαÎOcy/ÎOcy mice was significantly decreased. Bone formation parameters in ERαÎOcy/ÎOcy were significantly decreased while osteoclast parameters were unchanged. This suggests that ERα in osteocytes exerts osteoprotective function by positively controlling bone formation. To identify potential targets of ERα, gene array analysis of Dmp1-GFP osteocytes FACS sorted from ERαÎOcy/ÎOcy and control mice was performed. Expression of Mdk and Sostdc1, both known inhibitors of Wnt, were significantly increased without alteration of the mature osteocyte marker Sost or β-catenin. Hindlimb unloading exacerbated the trabecular bone loss, but surprisingly cortical bone was resistant. These studies show that ERα in osteocytes has osteoprotective effects in trabecular bone through regulating expression of Wnt antagonists, but conversely plays a negative role in cortical bone loss due to unloading. Wild type and osteocyte-specific Estrogen Receptor alpha knock-out mice were generated. The number of both genotypes of mice was three. Calvarial osteocytes of both genotypes harboring Dmp1-GFP were extracted by sequential enzymatic digestion, followed by FACS Aria sorting and total RNAs were purified for Affymetix GeneChip microarray analysis without pooling.
2013-12-12 | E-GEOD-41997 | biostudies-arrayexpress
Project description:Type of Experiment: 1) Profiles of Osteoblast vs. osteocyte in vitro; 2) Profiles of osteoblast low density vs. confluency in vitro; 3) Profiles of osteocyte with gap junction vs. without gap junction. Experimental factors: 1) 2T3 osteoblast cells at low density expressed extensive filopodia, reminiscent of early osteoblast precursors and similar to MLO-Y4 dendritic processes. 2) MLO-Y4 osteocytes at low vs. high density represent the genes that are changed in a highly connected network vs. low connected network. The number of hybridizations performed: Triplicate hybridizations for each status. Keywords = Osteoblast Keywords = Osteocyte
2010-06-09 | E-GEOD-2234 | biostudies-arrayexpress
Project description:Purpose of arrays were to determine what the effect of deletion of Mbtps1 gene was on gene expression of osteocytes in bone in vivo. DMP1 cre driver was used to delete the Mbtps1 gene in osteocytes and osteoblasts in bone. We then isolated osteocyte enriched bone particles from 40 week old male mice to determine the effect of this deletion on gene expression. We have previously shown that Mbtps1 is needed for transcription of Phex, DMP1, and MEPE genes in osteoblasts in culture. Arrays showed these genes were reduced as expected in osteocytes in vivo. Controls represent osteocyte enriched bone from 40 week old littermates. Also, as expected, Mbtps1 expression was reduced in these knockout mice
2015-12-29 | GSE69975 | GEO
Project description:Osteogenesis imperfecta (OI) is a group of diseases caused by defects in type I collagen processing which result in skeletal fragility. While these disorders have traditionally been regarded as defects in osteoblast function, the role of matrix-embedded osteocytes, descendants of osteoblasts, in OI pathogenesis remains unknown. The homozygous human SP7 (c.946C > T, R316C) mutation results in a recessive form of osteogenesis imperfecta characterized by short stature, fragility fractures, low bone mineral density, and osteocyte dendrite defects. To better understand how the osteogenesis imperfecta-causingSP7 R316Cmutation affects the function of this transcription factor in different osteoblast lineage cells in bone, we generatedSp7 R342Cknock-in mice. Homozygous mutantSp7 R342C/R342Cmice demonstrate increased cortical porosity and reduced cortical bone mineral density, findings consistent with phenotypes observed in patients with this mutation. Sp7 R342Cmice show osteocyte dendrite defects, increased osteocyte apoptosis, and intracortical bone remodeling characterized by ectopic intracortical osteoclasts and elevated Tnfsf11 expression by osteocytes. Remarkably, these overt defects in osteocyte function contrast to preserved osteoblast function, suggesting that this Sp7 point mutation selectively interferes with the function of this transcription factor in osteocytes but not osteoblasts. Osteocyte morphology changes in Sp7 R342C/R342Cmice were not restored by inhibiting osteoclast formation, indicating that dendrite defects lie upstream of high intra-cortical osteoclast activity in this model. Moreover, transcriptomic profiling reveals that the expression of a core set osteocyte-enriched genes is highly dysregulated by the R342C mutation. Thus, this model supports a model in which osteocyte dysfunction can drive osteogenesis imperfecta pathogenesis, and provides a valuable resource to test novel therapeutic approaches and to understand the osteocyte-specific role of SP7 in bone homeostasis and remodeling.
2025-05-16 | GSE270443 | GEO
Project description:Skeletal homeostasis if profoundly altered in response to multiple-myeloma tumour burden. Osteocytes are pivotal regulatory cells in skeletal homeostasis. This dataset was used to examine the differences in the osteocyte-specific transcriptome that may underlie the changes in skeletal homeostasis that occur with multiple myeloma tumour burden. We performed total-RNA transcriptome sequencing on the isolated osteocytes from tumour-burdened and naive bone samples, as well as the marrow from these samples. With this experimental design we can identify genes that are changed specifically in osteocytes in the presence of multiple myeloma tumour burden.
2023-12-31 | E-MTAB-5555 | biostudies-arrayexpress