Single cell sequencing shows that Sox9-expressing cells populate most mesenchymal lineages postnatally in mouse bone
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE259382 | GEO | 2025/03/03
REPOSITORIES: GEO
Similar Datasets
Project description:Chondrocytes advance through the long bone growth plate in synchrony, allowing their segregation into one of four zones each corresponding to a different phase of maturation. Beginning from the epiphysis the recognized zones are: reserve, proliferative, prehypertrophic, and hypertrophic. A fifth zone, the perichondrium is located in apposition to the growth plate at its circumferential surface. The progression of chondrocytes through these zones, and hence growth, is regulated by a complex interplay of signaling pathways, defects in which lead to osteochondrodysplasias. At present, there are over 370 recognized skeletal disorders, slightly more than half of which have been explained at the molecular level. Through a combination of laser microdissection, linear mRNA amplification, and GeneChip analysis, our laboratory has acquired the zone specific expression profile of chondrocytes from the distal femoral growth plates of two normal patients. On average, transcripts interrogated by 12,193 or 18,454 GeneChip probe sets (out of a possible 54,000 probe sets) were present in patients 1 and 2, respectively. The homologous inter-array correlations for the log(2) intensities were M-bM-^IM-% 0.91M-BM-10.01. Keywords: Chondrocyte differentiation program. Populations of cells corresponding to the hypertrophic, prehypertrophic, proliferative, reserve, and perichondrium, were separately isolated by laser microdissection from cryostat sections of human growth plates using a Leica AS-LMD microscope. RNA was prepared from the isolated cells, amplified using a T7 linear amplification protocol, and analyzed by hybridization to Affymetrix microarrays. The distal femoral growth plate (left or right) was exclusively used for this study. Patient 1 of this study is an 11-10/12 year old Caucasian female and patient 2 is a 13-3/12 year old Caucasian male.
2013-09-13 | E-GEOD-9160 | biostudies-arrayexpress
Project description:Bone homeostasis is regulated by hormones such as parathyroid hormone (PTH). While PTH can stimulate osteo-progenitor expansion and bone synthesis, how the PTH-signaling intensity in progenitors is controlled is unclear. Endochondral bone osteoblasts arise from perichondrium-derived osteoprogenitors and hypertrophic chondrocytes (HC). We found, via single-cell transcriptomics, HC descendent cells activate membrane-type 1 metalloproteinase 14 (MMP14) and the PTH pathway as they transition to osteoblasts in neonatal and adult mice. Unlike Mmp14 global knockouts, postnatal day 10 (p10) HC lineage-specific Mmp14 null mutants (Mmp14ΔHC) produce more bone. Mechanistically, MMP14 cleaves the extracellular domain of PTH1R, dampening PTH signaling, and consistent with the implied regulatory role, in Mmp14ΔHC mutants, PTH signaling is enhanced. We found HC-derived osteoblasts contribute ~50% of osteogenesis promoted by treatment with PTH 1-34 and this response was amplified in Mmp14ΔHC. MMP14 control of PTH signaling likely applies also to both HC- and non-HC-derived osteoblasts because their transcriptomes are highly similar. Our study identifies a novel paradigm of MMP14 activity-mediated modulation of PTH signaling in the osteoblast lineage, contributing new insights into bone metabolism with therapeutic significance for bone-wasting diseases.
2023-03-13 | GSE222203 | GEO
Project description:Chondrocytes advance through the long bone growth plate in synchrony, allowing their segregation into one of four zones each corresponding to a different phase of maturation. Beginning from the epiphysis the recognized zones are: reserve, proliferative, prehypertrophic, and hypertrophic. A fifth zone, the perichondrium is located in apposition to the growth plate at its circumferential surface. The progression of chondrocytes through these zones, and hence growth, is regulated by a complex interplay of signaling pathways, defects in which lead to osteochondrodysplasias. At present, there are over 370 recognized skeletal disorders, slightly more than half of which have been explained at the molecular level. Through a combination of laser microdissection, linear mRNA amplification, and GeneChip analysis, our laboratory has acquired the zone specific expression profile of chondrocytes from the distal femoral growth plates of two normal patients. On average, transcripts interrogated by 12,193 or 18,454 GeneChip probe sets (out of a possible 54,000 probe sets) were present in patients 1 and 2, respectively. The homologous inter-array correlations for the log(2) intensities were ≥ 0.91±0.01. Keywords: Chondrocyte differentiation program.
2013-09-13 | GSE9160 | GEO
Project description:C57BL/6 mice underwent early postnatal overfeeding by litter size reduction (3 pups/dam, instead of 10 pups/dam, in postatally normally fed mice). These overfeeding conditions lead to early and permanent modifications of body weight and to an increase in body fat mass in the adulthood. When these postnatally overfed mice become adult, they develop several cardio-metabolic alterations (mild hypertension, impairment of heart contractility, remodeling, fibrosis, hyperinsulinemia and hyperleptinemia) but also increases in markers of cardiac and plasma oxidative stress. Moreover, we observed a higher sensitivity of the heart to injuries induced by ischemia reperfusion, such as an increase in necrosis. We now aim to establish if these late-coming modifications might be induced in a very early state of postnatal development, such as a postnatal programming situation. To achieve this objective, we are now comparing heart gene expression between 24 days old postnatally overfed and normally fed mice. Comparison of heart gene expression between 24 days old postnatally overfed and normally fed mice.
2013-01-07 | E-GEOD-38995 | biostudies-arrayexpress
Project description:While prior work has established that articular cartilage arises from Prg4-expressing perichondrial cells, it is not clear how this process is specifically restricted to the perichondrium of synovial joints. We document that the transcription factor Creb5 is necessary to initiate the expression of signaling molecules that both direct the formation of synovial joints and guide perichondrial tissue to form articular cartilage instead of bone. Creb5 promotes the generation of articular chondrocytes from perichondrial precursors in part by inducing expression of Wif1, which blocks a Wnt5a autoregulatory loop in the perichondrium. Postnatal deletion of Creb5 in the articular cartilage leads to loss of both flat superficial zone articular chondrocytes coupled with a loss of both Prg4 and Wif1 expression; and a non-cell autonomous up-regulation of Ctgf. Our findings indicate that Creb5 promotes both joint formation and the subsequent development of articular chondrocytes by disrupting a Wnt5a positive-feedback loop in the perichondrium.
2022-11-07 | GSE181883 | GEO
Project description:Acute Crebbp knockout in postnatally induced Shh medulloblastoma [tumor]
| PRJNA419443 | ENA
Project description:C57BL/6 mice underwent early postnatal overfeeding by litter size reduction (3 pups/dam, instead of 10 pups/dam, in postatally normally fed mice). These overfeeding conditions lead to early and permanent modifications of body weight and to an increase in body fat mass in the adulthood. When these postnatally overfed mice become adult, they develop several cardio-metabolic alterations (mild hypertension, impairment of heart contractility, remodeling, fibrosis, hyperinsulinemia and hyperleptinemia) but also increases in markers of cardiac and plasma oxidative stress. Moreover, we observed a higher sensitivity of the heart to injuries induced by ischemia reperfusion, such as an increase in necrosis. We now aim to establish if these late-coming modifications might be induced in a very early state of postnatal development, such as a postnatal programming situation. To achieve this objective, we are now comparing heart gene expression between 24 days old postnatally overfed and normally fed mice.
2013-01-07 | GSE38995 | GEO
Project description:Gowth plate chondrocytes include heterogenous cell population and cellular diversity of these chondrocytes remains to be elucidated. We used single cell RNA sequencing to uncover the diverssity of growth plate chondrocytes and identify noel marker genes selectively expressed in pre-hypertrophic chondrocytes.
2024-11-21 | GSE271634 | GEO
Project description:Polycomb repressive complex 2 (PRC2) controls maintenance and lineage determination of stem cells by suppressing genes that regulate cellular differentiation and tissue development. However, the role of PRC2 in lineage-committed somatic cells is largely unknown. In this study, we ablated Eed, an essential component of PRC2, in growth plate chondrocytes to study the role of PRC2 in skeletal development. In this study, we profiled genes assocaited with H3K27me3 histone 3 modification in primary rib chondrocytes.
2016-04-01 | GSE76467 | GEO
Project description:Fetal bone development occurs by endochondral conversion of avascular cartilage to vascularized bone at the growth plate. This requires coordinated mobilization of osteoblast precursors with blood vessels. In adult bone, vessel-adjacent osteoblast precursors are maintained by mechanical stimuli; however, the mechanisms by which these cells mobilize and respond to mechanical cues during embryonic development are unknown. Here, we unify osteoblast precursor co-mobilization and mechanotransduction in a single signaling pathway, via the mechanosensitive transcriptional regulators YAP and TAZ. We show that YAP and TAZ spatially couple osteoblast precursor mobilization to angiogenesis, regulate vascular loop morphogenesis to control growth plate remodeling, and mediate mechanoregulation of load-induced osteogenesis in embryonic bone. Mechanistically, YAP and TAZ uniquely regulate a subset of osteoblast-lineage cells, identified by single-cell RNA sequencing as vessel-associated osteoblast precursors. Among these cells, YAP and TAZ regulate expression of the angiogenic chemokine, Cxcl12. Functionally, in 3D human cell co-culture, CXCL12 treatment rescued angiogenesis impaired by stromal cell YAP/TAZ depletion. Together, these data establish new functions of the vessel-associated osteoblast precursors in endochondral bone development.
2023-11-15 | GSE227818 | GEO