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A supporting environment for hematopoietic stem/progenitor cells is maintained by canonical Wnt signaling

ABSTRACT: Considerable information has accumulated about components of bone marrow that regulate survival, self-renewal and differentiation of hematopoietic cells. We have now studied Wnt signaling in that context, assessing influences on human and murine hematopoiesis. Microarray, PCR and staining experiments revealed that OP9 acquired osteoblastic characteristics while down-regulating some features associated with mesenchymal stem cells. This included down-regulation of Angiopoietin 1, c-Kit ligand and VCAM-1 expression. In contrast, production of decorin, tenascins and fibromodulin markedly increased. At least one of these extracellular matrix components, decorin is a regulator of hematopoiesis. That is, addition of the protein to OP9 co-cultures causes changes similar to Wnt3a.

ORGANISM(S): Mus musculus

PROVIDER: GSE30791 | GEO | 2012/03/14

SECONDARY ACCESSION(S): PRJNA144287

REPOSITORIES: GEO

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A supporting environment for hematopoietic stem/progenitor cells is maintained by canonical Wnt signaling

Project description:Considerable information has accumulated about components of bone marrow that regulate survival, self-renewal and differentiation of hematopoietic cells. We have now studied Wnt signaling in that context, assessing influences on human and murine hematopoiesis. Microarray, PCR and staining experiments revealed that OP9 acquired osteoblastic characteristics while down-regulating some features associated with mesenchymal stem cells. This included down-regulation of Angiopoietin 1, c-Kit ligand and VCAM-1 expression. In contrast, production of decorin, tenascins and fibromodulin markedly increased. At least one of these extracellular matrix components, decorin is a regulator of hematopoiesis. That is, addition of the protein to OP9 co-cultures causes changes similar to Wnt3a. Two control samples (LZR1 & LZR2) were analyzed from OP9 mouse stromal cells transfected with vector only, and two experimental samples (W3A1 & W3A2) were analyzed from OP9 cells transfected with vector containing the Wnt3A gene.

2012-03-14 | E-GEOD-30791 | biostudies-arrayexpress

Transcription profiling of mouse aorta-gonad-mesonephros(AGM) derived stromal cells

Project description:A mouse AGM-derived cell line, AGM-s3, was shown to support the development of hematopoietic stem cells. To elucidate the molecular mechanisms regulating early hematopoiesis, we obtained subclones from AGM-s3, some of which were hematopoiesis supportive (s3-A9) and others which were non-supportive (s3-A7), and we analyzed the gene expression profiles by gene chip analysis. Experiment Overall Design: Genome-wide gene expression was examined using Affymetrix GeneChip array. Assays were performed according to the manufacturer's protocol. Total RNA was isolated from each stromal cell lines. We analysed 3 cell lines, AGM-s3-A9, AGM-s3-A7 and OP9. AGM-s3-A9 and OP9 are hematopoiesis supportive cell lines. AGM-s3-A7 is a hematopoiesis non-supportive cell line.

2008-10-26 | E-GEOD-11891 | biostudies-arrayexpress

Global RNA expression of fibromodulin reprogrammed human BJ fibroblasts

Project description:RNA-seq analysis of fibromodulin reprogrammed human BJ fibroblasts to obtain the global transcripton of the yield fibromodulin reprogrammed (FReP) cells.

2019-08-10 | GSE104830 | GEO

A Notch ligand, Delta-like 1 functions as an adhesion molecule for mast cells

Project description:To assess the effect of over-expression of Delta-like 1 on OP9 cells on gene expression in terms of Notch signaling and adhesion molecules, gene expressions of OP9, OP9-GFP (carrying GFP gene) and OP9-DL1 (carrying GFP and DL1 gene) cells (Immunity 2002;17:749-756) were analyzed.

2010-10-01 | GSE22659 | GEO

Collagen I and fibromodulin induce tenogenic differentiation of hASCs

Project description:Collagen I and fibromodulin, which was immobilized on PLCL nanoyarn, induced tenogenic differentiation of hASCs

2024-01-02 | GSE246270 | GEO

The proteome of normal human sclera

Project description:The sclera provides an opaque protective coat for five-sixths of the surface of the human eye. A detailed investigation of the proteome of the normal human sclera may provide insights into the biology and pathophysiology of the sclera. We conducted an in-depth proteomic analysis of sclera from five adults. Proteins were fractionated using SDS-PAGE. After in-gel digestion, peptides were analyzed using LC-MS/MS on an Orbitrap Elite mass spectrometer. We identified 1952 non-redundant proteins in the human sclera, including 18 different collagen protein chains (types 1, II, III, IV, VI, VIII, X, XII, XIV, XV, XVI, XVIII), proteins of the small leucine-rich proteoglycan family (decorin, biglycan, lumican, keratocan, prolargin, fibromodulin, and mimecan), non-collagenous glycoproteins (fibronectin, vitronectin, and laminin), extracellular matrix proteins (thrombospondins 1, 2, 3, 4, dystroglycan, and transgelins 1, 2, 3), matrix metalloproteinases 3 and 14, matrix metalloproteinase inhibitors 1, 2, and 3, and integrins alpha-V, alpha-1, alpha-2, beta-1, beta-2, and beta-5.

2022-03-01 | PXD004223 | Pride

Transcription profiling of rat cirrhotic liver treated with angiogenesis inhibitors

Project description:Background and aims: There are considerable evidences demonstrating that angiogenesis and chronic inflammation are mutually dependent. However, although cirrhosis progression is characterized with a chronic hepatic inflammatory process, this connection is not sufficiently explored as a therapeutic strategy. Therefore, this study was aimed to assess the potential benefits of targeting angiogenesis in cirrhotic livers to modulate inflammation and fibrosis. For this purpose, we evaluate the therapeutic utility of angiogenesis inhibitors. Methods: The in vivo effects of angiogenesis inhibitors were monitored in liver of cirrhotic rats by measuring angiogenesis, inflammatory infiltrate, fibrosis, a-smooth muscle actin (a-SMA) accumulation, differential gene expression (by microarrays), and portal pressure. Results: Cirrhosis progression was associated with a significant enhancement of vascular density and expression of vascular endothelial growth factor-A (VEGF-A), angiopoietin-1, angiopoietin-2 and placental growth factor (PlGF) in cirrhotic livers. The newly formed hepatic vasculature expressed vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Interestingly, the expression of these adhesion molecules correlated well with local inflammatory infiltrate. Livers of cirrhotic rats treated with angiogenesis inhibitors presented a significant decrease in hepatic vascular density, inflammatory infiltrate, a-SMA abundance, collagen expression and portal pressure. Conclusion: Angiogenesis inhibitors may offer a potential novel therapy for cirrhosis due to its multiple mechanisms of action against angiogenesis, inflammation and fibrosis in cirrhotic livers. Experiment Overall Design: RNA from liver of 4 non-treated cirrhotic rats or 4 rats treated with angiogenesis inhibitors was hybridized to 8 high-density oligonucleotide microarray (Rat2302, Affymetrix, Santa Clara, CA)

2008-06-15 | E-GEOD-6929 | biostudies-arrayexpress

Frizzled receptors facilitate Tiki inhibition of Wnt signaling at the cell surface

Project description:Tiki antagonizes Wnt3a signaling by cleaving and inactivating Wnt3a in Wnt-producing cells. Tiki also functions in Wnt-receiving cells to antagonize Wnt signaling by an unknown mechanism. Here, we demonstrate that Tiki inhibition of Wnt signaling at the cell surface requires Frizzled receptors. Tiki associates with the Wnt-FZD complex and cleaves the N-terminus of Wnt3a or Wnt5a, preventing the Wnt-FZD complex from recruiting and activating the coreceptor LRP6 or ROR1/2 without affecting Wnt-FZD complex stability. Intriguingly, we demonstrate that the N-terminus of Wnt3a is required for Wnt3a binding to LRP6 and activating β-catenin signaling, while the N-terminus of Wnt5a is dispensable for recruiting and phosphorylating ROR1/2. Both Tiki enzymatic activity and its association with the Wnt-FZD complex contribute to its inhibitory function on Wnt5a. Our study uncovers the mechanism by which Tiki antagonizes Wnt signaling at the cell surface and reveals a negative role of FZDs in Wnt signaling by acting as Tiki cofactors. Our findings also reveal an unexpected role of the Wnt3a N-terminus in the engagement of the coreceptor LRP6.

2023-05-24 | PXD040942 | Pride

Gene expression profile at single cell level of crude umbilical cord blood (UCB) and OP9 pre-conditioned UCB.

Project description:Umbilical cord blood (UCB) transplantation shows pro-angiogenic effect and contributes to symptom amelioration in animal models of cerebral infarction. OP9 is a stromal cell line used as feeder cells to promote hematoendothelial differentiation of embryonic stem cells. We co-cultured UCB 24hr with OP9 (i.e. OP9 preconditioning) and investigated its change in angiogenic properties and underlying mechanisms. Single cell RNA sequencing showed prominent phenotypic shift toward M2 in monocytic fraction of OP9 pre-conditioned UCB.

2023-01-25 | GSE207249 | GEO

Mouse Bone-marrow Stromal Cell Lines Genetic Expression Comparison

Project description:OP9 stromal cells are strong inducers of mesoendodermal differentiation of human embryonic stem cells. They acquire inductive function after prolonged post-confluence culture. The experiment is designed to determine the genes specifically expressed in these highly inductive OP9 cells compared to non-confluent OP9 cultures as well as other stromal cell lines (MS5, S17).

2014-09-20 | GSE61580 | GEO

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