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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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RNA sequencing of primary thymic, bone and skin mesenchymal cells

ABSTRACT: Purpose : Elucidate post-natal role of SCA1+ thymic mesenchymal cells (tMCs) and evaluate the functional overlap between thymic, bone and skin MCs. Method : By high speed cell sorting, we isolated primary MCs (Lin- SCA1+ cells) from mouse thymus, bone and skin. We extracted their respective total RNA and compared their transcriptome by high-throughput RNA-sequencing. Results : We found a total of 2036 differentially expressed genes (FC>5, p-adj<0.1 and RPKM>1) between the 3 MC populations. IPA analyses revealed that each MC population was enriched for genes associated to phagocyte chemotaxis. We also denoted 2850 genes with shared expression across MC populations. IPA analysis of those shared genes also revealed an enrichment for genes influencing phagocyte migration, chemotaxis and function. Finally, MC transcriptomes showed that all 3 MC populations were expressing genes associated with hematopoietic stem and progenitor cell (HSPC) support, strongly suggesting that MCs from thymic, bone and skin all possess the ability to support HSPCs. Conclusion : Overall, our study highlighted 3 potential novel roles for tMCs : 1) Promoting macrophage/monocyte chemotaxis, 2) Enhacing the apoptotic cell clearance process and 3) setting an inviting niche for hematopoietic progenitors. These novel biological roles for tMCs could have substantial effets on thymic biology. Finally, our RNA-seq data offer a valuable resource to the community that can be mined to explore multiple questions related mesenchymal cell biology. Transcriptome comparison between MC populations

ORGANISM(S): Mus musculus

SUBMITTER: Julien Patenaude

PROVIDER: E-GEOD-73175 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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CINC-2 and miR-199a-5p in exosomes secreted by transplanted Thy1+ cells activate hepatocytic progenitor cell growth in rat liver regeneration

Project description:Small hepatocyte-like progenitor cells (SHPCs) are hepatocytic progenitor cells that transiently form clusters in rat livers treated with retrorsine and with 70% partial hepatectomy (PH). We previously reported that transplantation of Thy1+ cells derived from D-galactosamine-treated livers promotes SHPC expansion, resulting in the acceleration of liver regeneration. Extracellular vesicles (EVs) produced by Thy1+ cells act on sinusoidal endothelial cells (SECs) and Kupffer cells to secrete IL17B and IL25, respectively, resulting in SHPC activation through IL17 receptor B (RB) signaling. Our aim is to identify factors in Thy1-EVs that activate IL17RB signaling. Thy1+ cells isolated from rats with D-galactosamine-induced liver injury were cultured for one week. Although some liver stem/progenitor cells proliferated into colonies, others maintained as mesenchymal cells (MCs). Thy1-MCs or Thy1-liver stem/progenitor cells were transplanted into retrorsine/PHtreated livers to examine their effects on SHPCs. SHs isolated from adult rat livers were used to validate factors regulating growth induction. The number and size of SHPCs remarkably increased in livers transplanted with Thy1-MCs. Comprehensive analysis of Thy1-MC-EVs revealed that miR-199a-5p, CINC-2, and MCP-1 are candidates for stimulating SHPC growth. Administration of the miR-199a-5p mimic, and not CINC-2, promoted SH growth. SECs treated with CINC-2 induced IL17b expression and their conditioned medium promoted SH growth. Thy1-MC transplantation may accelerate liver regeneration due to SHPCs expansion, which is stimulated by CINC-2/IL17RB signaling and miR-199a-5p.

2023-04-07 | PXD039384 | Pride

Role of adhesion receptors in mast cell disease-evolution

Project description:Systemic mastocytosis (SM) is an incurable neoplasm characterized by abnormal accumulation of neoplastic mast cells (MC) in vascularized organs. In indolent SM, MC express several different adhesion-molecules including CD2 and CD58, and form focal tissue-aggregates, whereas in advanced SM, MC often lack CD2 and produce a more diffuse infiltration-pattern. To explore the functional role of CD2 in the pathology of SM, stable CD2+ and CD2− subclones of the human MC-leukemia cell line HMC-1 were generated and injected intraperitoneally into pfp/rag2 mice. CD2+ HMC-1 cells formed solid mastocytomas in the peritoneum and lungs, whereas CD2− cells produced diffuse infiltration. CD2+ and CD2− HMC-1 subclones all displayed the driver-mutant KIT D816V, exhibited the same growth-kinetics, and displayed identical adhesion-receptors including CD44 and selectin-ligands. To explore the mechanism of organ invasion, E- and P-selectin-deficient scid mice (scid-select) were employed. While massive HMC-1 infiltrates were detected in the lungs of control mice, infiltration was markedly reduced or absent in scid-select mice. The invasion-receptor CD44 was detectable in all MC infiltrates, with most abundant expression in the invasion-front. Together, our data show that selectins mediate organ-invasion of MC and CD2-CD58 interactions contribute to a more focal infiltration-pattern which is lost during progression to MC leukemia. HMC1 cells were sorted by FACS for expression of CD2 surface expression. 2 subclones were obtained (CD2+ or CD2-) and compared by gene expression profiling using U133 plus 2.0 GeneChips

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RNA sequencing of primary thymic, bone and skin mesenchymal cells

Project description:Purpose : Elucidate post-natal role of SCA1+ thymic mesenchymal cells (tMCs) and evaluate the functional overlap between thymic, bone and skin MCs. Method : By high speed cell sorting, we isolated primary MCs (Lin- SCA1+ cells) from mouse thymus, bone and skin. We extracted their respective total RNA and compared their transcriptome by high-throughput RNA-sequencing. Results : We found a total of 2036 differentially expressed genes (FC>5, p-adj<0.1 and RPKM>1) between the 3 MC populations. IPA analyses revealed that each MC population was enriched for genes associated to phagocyte chemotaxis. We also denoted 2850 genes with shared expression across MC populations. IPA analysis of those shared genes also revealed an enrichment for genes influencing phagocyte migration, chemotaxis and function. Finally, MC transcriptomes showed that all 3 MC populations were expressing genes associated with hematopoietic stem and progenitor cell (HSPC) support, strongly suggesting that MCs from thymic, bone and skin all possess the ability to support HSPCs. Conclusion : Overall, our study highlighted 3 potential novel roles for tMCs : 1) Promoting macrophage/monocyte chemotaxis, 2) Enhacing the apoptotic cell clearance process and 3) setting an inviting niche for hematopoietic progenitors. These novel biological roles for tMCs could have substantial effets on thymic biology. Finally, our RNA-seq data offer a valuable resource to the community that can be mined to explore multiple questions related mesenchymal cell biology.

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2015-05-08 | E-GEOD-68668 | biostudies-arrayexpress

The Inhibitory Receptor Siglec-8 Interacts with FcεRI and Globally Inhibits Intracellular Signaling in Primary Mast Cells Upon Activation

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2022-01-21 | PXD030820 | Pride

Gene expression data of human peripheral blood-derived cultured mast cells

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