Delineation of cellular niches which support hematopoiesis in spleen
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Hematopoietic stem cell (HSC) niches in bone marrow have been described in terms of distinct cell types including osteoblastic, endothelial and perivascular reticular cells. However, niches which support extramedullary hematopoiesis in other sites like spleen remain to be elucidated. Previous studies have described splenic stromal cells which support hematopoiesis in vitro from purified HSC and multipotential progenitors (MPP) leading to the production of dendritic-like cells. Stromal cell lines were originally derived from splenocyte cultures, and later as freshly isolated stromal subsets prepared by enzymatic digestion and sorting. Transcriptome analysis has revealed that stroma which support hematopoiesis express many genes in parallel with perivascular cells described in bone marrow. They share a common mesenchymal lineage with perivascular cells in bone marrow, as well as mesenchymal progenitor cells and CXCL12-abundant reticular cells. They reflect osteoprogenitors in that cells can be induced to osteogenesis, although not adipogenesis or chondrogenesis, when cultured in defined media. Cell surface markers common to these cells include CD105, CD29, VCAM1, CD51, CD140a/b and CD90. A number of new markers and genes have been identified which delineate this cell type and determine their ability to support hematopoiesis. These studies have employed inhibitors and gene knockdown to block stromal cell signaling and interaction with HSC in order to identify novel regulators of in vitro hematopoiesis.
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