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Global transcriptome analysis of T-competent progenitors in the bone marrow.

ABSTRACT: T cells are known to develop in the thymus. However, molecular events that control the transition from hematopoietic progenitor cells in the bone marrow to T precursor cells seeded in the thymus remained poorly defined. Our recent report showed that osteocalcin (Ocn)-expressing bone cells in the bone marrow have major impact on T cell immunity by regulating T progenitor development in the bone marrow (Yu et al., 2015) [1]. Selective endogenous depletion of Ocn(+) cells by inducible diphtheria toxin receptor expression (OcnCre;iDTR) led to reduction of T-competent common lymphoid progenitors (Ly6D(-) CLPs) in the bone marrow and loss of T cells in the thymus. Expression of the Notch ligand DLL4 by Ocn(+) cells in the bone marrow ensures the production of Ly6D(-) CLPs, and expression of chemotactic molecules CCR7 and PSGL1 to enable subsequent thymic seeding. These data indicate that specific mesenchymal cells in bone marrow provide key molecular drivers enforcing thymus-seeding progenitor generation and thereby directly link skeletal biology to the production of T cell based adaptive immunity. Here we present the transcriptome profiles of Ly6D(-) CLPs derived from Ocn(+) cells deleted mice (OcnCre(+);iDTR) compared to those derived from control littermates (OcnCre(-);iDTR). These data are publically available from NCBI Gene Expression Omnibus (GEO) with the accession number GSE66102.

SUBMITTER: Yu VW

PROVIDER: S-EPMC4583637 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Global transcriptome analysis of T-competent progenitors in the bone marrow.

Yu Vionnie W C VW Scadden David T DT

Genomics data 20150605

T cells are known to develop in the thymus. However, molecular events that control the transition from hematopoietic progenitor cells in the bone marrow to T precursor cells seeded in the thymus remained poorly defined. Our recent report showed that osteocalcin (Ocn)-expressing bone cells in the bone marrow have major impact on T cell immunity by regulating T progenitor development in the bone marrow (Yu et al., 2015) [1]. Selective endogenous depletion of Ocn(+) cells by inducible diphtheria to ...[more]

PMID: 26484235

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Project description:Abstract Background: Bone marrow stromal cells (BMSCs) are being used for immune modulatory, anti-inflammatory and tissue engineering applications, but the properties responsible for these effects are not completely understood. Human BMSCs were characterized to identify factors that might be responsible for their clinical effects and biomarkers for assessing their quality. Methods: Early passage BMSCs prepared from marrow aspirates of 4 healthy subjects were compared to 3 human embryonic stem cell (hESC) samples, CD34+ cells from 3 healthy subjects and 3 fibroblast cell lines. The cells were analyzed with oligonucleotide expression microarrays with more than 35,000 probes. Results: BMSC gene expression signatures of BMSCs differed from those of hematopoietic stem cells (HSCs), hESCs and fibroblasts. Genes up-regulated in BMSCs were involved with cell movement, cell-to-cell signaling and interaction and proliferation. The BMSC up-regulated genes were most likely to belong to integrin signaling, integrin linked kinase (ILK) signaling, NFR2-mediated oxidative stress response, regulation of actin-based motility by Rho, actin cytoskeletal signaling, caveolar-mediated endocytosis, clathrin-mediated endocytosis and Wnt/beta catenin signaling pathways. Among the most highly up-regulated genes were structural extracellular (ECM) proteins: alpha1 and beta1 integrin chains, fibronectin, collagen type IIIalpha1, and collagen type Valpha1 and functional EMC proteins: connective tissue growth factor (CTGF) and transforming growth factor beta induced protein (TGFBI) and ADAM12. Conclusions: Global analysis of human BMSCs suggests that they are mobile, metabolically active, proliferative and interactive cells that make use of integrins and integrin signaling. They produce abundant ECM proteins; some of which may contribute to their clinical immune modulatory and anti-inflammatory effects. Seven samples from early passage BMSCs were prepared from marrow aspirates of healthy subjects and compared to 3 human embryonic stem cell (hESC) samples, CD34+ cells from 3 healthy subjects and 3 fibroblast cell lines. Total RNA from a pool of PBMCs from six healthy subjects was extracted and amplified into aRNA to serve as a reference.

Dataset Information

Global transcriptome analysis of T-competent progenitors in the bone marrow.

Publications

Global transcriptome analysis of T-competent progenitors in the bone marrow.

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