Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spleen stromal cells are critical determinants of dendritic cell (DC) development in spleen. The spleen stromal line, namely STX3, supports DC differentiation in vitro from overlaid bone marrow cells while the lymph node stromal line, namely 2RL22, does not. Here we have characterised the hematopoietic support capacity of each stroma, and analysed lineage origin of the stromal cell lines by gene profiling using microarrays. Stromal co-culture experiments were performed using bone marrow cells as a source of hematopoietic progenitors. A characteristic immature myeloid-like CD11c(+)CD11b(+)CD86(+)MHC-II(/lo)B220()CD8alpha() DC is produced after 14 days in STX3 cocultures, while 2RL22 cocultures produce only monocyte/macrophage-like cells. No other hematopoietic cell type is produced. The STX3 and 2RL22 stroma were compared by transcriptome analysis utilising Affymetrix Murine U74Av2 genechips to identify gene expression related to differential hematopoietic support function. Data mining was used to determine cell surface marker expression reflecting endothelial cells and fibroblasts, as well as adhesion molecules contributing to the microenvironment. STX3 shows gene expression reflective of early endothelial cells, while 2RL22 expresses markers specific to fibroblasts. The expression of genes like Flt1, CD34, Mcam, and Eng distinguishes STX3 as an early immature endothelial cell lacking markers of angioblasts or hemangioblasts like Tal1/SCL, Tie1, Tie2, Kdr or Prom1/AC133. The absence of expression of genes like Vwf and Cd31 distinguishes STX3 from fully differentiated vascular endothelial cells. In contrast, the 2RL22 lymph node stroma specifically expresses genes related to fibroblastic-like cells like osteoblasts with expression of Vdr (Vitamin D receptor), and epithelial cells with expression of Krt13 (keratins). Gene expression data identifies STX3 as splenic endothelial cells, independently able to support the outgrowth of immature, myeloid DC-like cells from progenitors present in bone marrow, while 2RL22 lymph node fibroblastic cells provide support for development of monocytes/macrophages.
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PMID:Gene signature of stromal cells which support dendritic cell development. 1856 35

Spleen and bone marrow (BM) have been shown to contain the progenitors of a novel dendritic-like antigen-presenting cell type (L-DC). These progenitors are also maintained in both long-term spleen cultures and co-cultures of spleen or BM over the stromal cell line STX3. We examined mouse foetal liver (FL), rich in hematopoietic stem/progenitor cells (HSC/HPC) after embryonic day (E) 12.5, for the presence of L-DC progenitors by testing their capacity to colonize STX3 and produce L-DC. E14.5 FL from wild-type C57BL/6J mice was found to colonize STX3 and produce L-DC for 28 days. By contrast, E14.5 FL from Ikaros Plastic mice gave only short-term production of low numbers of L-DC between 7 and 14 days of co-culture. The transient and weak production of L-DC by FL from Plastic E14.5 mice maps to the loss of self-renewal capacity amongst HSC. L-DC progenitors are, therefore, closely aligned with a subset of self-renewing HSC/HPC in FL.
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PMID:Distinct In Vitro Myelopoiesis is Dependent on the Self-Renewal of Hematopoietic Progenitors. 2195 39