Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Novel Osteoclastic Network Determines Niche for Mouse Hematopoietic Stem Cells In Vitro

ABSTRACT: The importance of extrinsic regulation of hematopoietic stem cell activity is increasingly acknowledged. Here we report the generation of a new niche system, which supports expansion of mouse hematopoietic stem cells in vitro. Characterization of this niche revealed a transcriptional regulatory network including four critical factors, namely FOS, SPI1, KLF10 and TFEC. Interestingly, these factors are essential for osteoclastogenesis, thus revealing an osteoclastic network that supports hematopoietic stem cell self-renewal.

ORGANISM(S): Mus musculus

PROVIDER: GSE39835 | GEO | 2013/12/31

SECONDARY ACCESSION(S): PRJNA171826

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

A Novel Osteoclastic Network Determines Niche for Mouse Hematopoietic Stem Cells In Vitro

Project description:The importance of extrinsic regulation of hematopoietic stem cell activity is increasingly acknowledged. Here we report the generation of a new niche system, which supports expansion of mouse hematopoietic stem cells in vitro. Characterization of this niche revealed a transcriptional regulatory network including four critical factors, namely FOS, SPI1, KLF10 and TFEC. Interestingly, these factors are essential for osteoclastogenesis, thus revealing an osteoclastic network that supports hematopoietic stem cell self-renewal. Lentiviral vectors containing putative transcription factors regulating HSC expansion were transfected into GPE cells and gene expression values were compared to empty vector controls.

2013-12-31 | E-GEOD-39835 | biostudies-arrayexpress

Mus musculus

Project description:A Novel Osteoclastic Network Determines Niche for Mouse Hematopoietic Stem Cells In Vitro

| PRJNA171826 | ENA

Transcription profiling of human osteoclastic differentiating from dendritic cells or monocytes

Project description:Comparison of osteoclastic differentiation pathway from DCs with the canonical differentiation pathway from monocytes by transcriptomic profiling

2009-09-01 | E-MEXP-2019 | biostudies-arrayexpress

Osteoclastic estrogen receptor alpha mediates the osteoprotective estrogen action through Fas ligand signaling

Project description:Estrogen clearly prevents osteoporotic bone loss by attenuating bone resorption. The molecular basis of how this is accomplished, however, remains elusive. Here we report a critical role of osteoclastic ERa in mediating estrogen action on bone in females. We selectively ablated ERa in differentiated osteoclasts (ERa dOc/dOc). ERa dOc/dOc females, but not males, exhibited clear trabecular bone loss, similar to the osteoporotic bone phenotype in post-menopausal women. Recovery of bone loss by estrogen treatment of the ovariectomized ERa dOc/dOc females was ineffective in the trabecular areas of the long bones and lumbar vertebral bodies. Osteoclastic apoptosis, induced by estrogen, occurred simultaneously with up-regulation of Fas ligand (FasL) expression in intact trabecular bones of ERa +/+mice, but not in ERa dOc/dOc mice. ERa was also required for similar effects of estrogen and tamoxifen in cultured osteoclasts. These findings suggest that the osteoprotective actions of estrogen and SERMS are mediated at least in part through osteoclastic ERa in trabecular bone; and the life span of mature osteoclasts is regulated through activation of the Fas/FasL system. Keywords: Study about estrogen response of osteoclast-specific estrogen receptor alpha mice

2007-06-01 | GSE7798 | GEO

Transcriptional deregulation during osteoclastic differentiation due to diuron exposure affects preferentially super-enhancers regulated genes

Project description:Osteoclasts are major actors in the maintenance of bone homeostasis. The full functional maturation of osteoclasts from monocyte lineage cells is essential for the degradation of old/damaged bone matrix. To better characterize the differentiation and maturation of CD14+ monocytes into functionally mature osteoclasts, we performed Chromatin Immunoprecipitation against H3K27ac followed by Sequencing (ChIP-Seq) and RNA-Sequencing at different stages of an in vitro differentiation model. The combinatorial study of the epigenetic and transcriptional dynamics taking place during the course of differentiation has allowed us to reveal a very dynamic epigenetic profile that supports the expression of genes vital for osteoclasts differentiation and function. In total, we identified 122 genes induced by dynamic super-enhancers at late days. Since diuron, a commonly detected herbicide in our environment, is suspected to affect bone development, we then sought to evaluate the potential impact of diuron exposure on bone homeostasis. We performed RNA-Seq and functional test during in vitro osteoblastic and osteoclastic differentiation. First of all, our data suggest that high-dose of diuron (50 µM) affects viability of mesenchymal stem cells and thus inhibits bone mineralization. We observed at lower dose (1 µM) an inhibitory effect of this herbicide on number of osteoclasts derived from CD14+ monocytes without affecting cell viability. RNA-Seq data analysis revealed that diuron is specifically affecting the transcriptional network dedicated to osteoclasts differentiation and activity. Among the diuron affected genes, our analysis suggests a significant enrichment of genes targeted by gained super-enhancers along the differentiation process, with an odds ratio of 5.12 (ρ = 2.59 x 10-5). Taken together our results suggest that diuron exposure disrupts osteoclasts maturation by impairing the expression of cell-identity determining genes.

2023-06-21 | GSE178196 | GEO

Osteomacs promote maintenance of murine hematopoiesis through megakaryocyte-induced upregulation of Embigin and CD166

Project description:Maintenance of hematopoietic stem cell (HSC) function in the niche is an orchestrated event. Osteomacs (OM), are key cellular components of the niche. Previously, we documented that osteoblasts, OM, and megakaryocytes interact to promote hematopoiesis. Here, we further characterize OM and identify megakaryocyte-induced mediators that augment the role of OM in the niche. Single cell mRNAseq, mass spectrometry, and CyTOF examination of megakaryocyte-stimulated OM suggested that upregulation of CD166 and Embigin on OM augment their hematopoiesis maintenance function. CD166 knockout OM or shRNA-Embigin knockdown OM, confirmed that loss of these molecules significantly reduced OM ability to augment the osteoblast-mediated hematopoietic enhancing activity. Recombinant CD166 and Embigin partially substituted for OM function, characterizing both proteins as critical mediators of OM hematopoietic function. Our data identify Embigin and CD166 as OM-regulated critical components of HSC function in the niche and potential participants in various in vitro manipulations of stem cells.

2024-01-11 | MSV000093840 | MassIVE

KLF10 modulates stem cell phenotypes of pancreatic adenocarcinoma by transcriptionally regulating notch receptors

Project description:KrÜppel-like factor 10 (KLF10), deficient in two thirds of 105 resected pancreatic adenocarcinoma (PDAC) patients, was associated with rapid loco-regional recurrence and large tumor size. Additional KLF10 depletion in KC (LSL: KrasG12D; Pdx1-CRE) mice accelerated progression from pancreatic intraepithelial neoplasia to PDAC. In Panc-1 cells with KLF10 deficiency (Panc-1-pLKO-shKLF10), increased sphere formation, stem cell markers expression, and tumor growth were noted compared with those of control. Over-expressing KLF10 genetically or pharmacologically using metformin, reversed the stem cell phenotypes induced by KLF10 depletion. Ingenuity pathway analysis and gene set enrichment analysis showed Notch signal molecules including Notch receptors 3 and 4 were over-expressed in Panc-1-pLKO-shKLF10. KLF10 transcriptionally suppressed Notch 3 and 4 receptors by competing with ELF3, a positive regulator, for promoter binding. Downregulating Notch signal genetically or pharmacologically ameliorated stem cell phenotypes of Panc-1-pLKO-shKLF10. Elevating KLF10 expression by metformin with concomitant evodiamine, a non-toxic Notch 3 methylation stimulator, delayed murine tumor growth of PDAC with KLF10 deficiency without prominent toxicity. These results demonstrated a novel signal pathway of KLF10 in modulating stem cell phenotypes of PDAC via transcriptional regulating Notch signal pathway. Elevating KLF10 and suppressing Notch signal may cooperatively reduce PDAC tumorigenesis and malignant progression.

2023-06-21 | GSE218172 | GEO

Mitochondrial regulation of bone homeostasis via mitochondria transfer [RNA-seq]

Project description:Recent studies have demonstrated that mitochondria can be transferred between different cell types to control metabolic homeostasis. However, whether the mitochondria transfer network occurred in the skeletal system or regulate skeletal metabolic homeostasis in vivo is not fully elucidated. Herein, we found that osteolineage cells transfer mitochondria to CD11b+ myeloid, B220+ lymphoid and hematopoietic stem and progenitor cells (HSPCs), of which monocytes/macrophages received the most transferred mitochondria. This process was inhibited by GC treatment contributing to the progression of glucocorticoid-induced osteoporosis (GIOP). Further analysis demonstrated that osteolineage cells transfer mitochondria to osteoclastic lineage cells via Miro1 mediated direct contact, and altered the glutathione metabolism, leading to the ferroptosis of osteoclastic lineage cells, thus inhibiting osteoclast activities. These findings revealed an unappreciated mechanism of mitochondrial regulation of skeletal metabolic homeostasis via mitochondria transfer and provide new insights of the mechanism of GIOP progression.

2024-04-08 | GSE225414 | GEO

Secretome Comparison of Mesenchymal Stromal Cells and Immature Osteoblasts

Project description:Osteoblasts are a key component of the endosteal hematopoietic stem cell (HSC) niche and have long been recognized with strong hematopoietic supporting activity. Osteoblast conditioned media (OCM) enhances the growth of hematopoietic progenitors in culture and modulate their engraftment activity. We aimed to characterize the hematopoietic supporting activity of OCM by comparing the secretome of immature osteoblasts to that of their precursor, mesenchymal stromal cells (MSC). Over 300 secreted proteins were quantified by mass spectroscopy in media conditioned with MSC or osteoblasts, with 47 being differentially expressed.

2020-07-17 | PXD017372 | Pride

Identification of a novel role for FoxO3 isoform2 in osteoclastic inhibition

Project description:Identification of a novel role for FoxO3 isoform2 in osteoclastic inhibition

| PRJNA559068 | ENA