HEMATOPOIESIS AND STEM CELLS Delineation of precursors in murine spleen that develop in contact with splenic endothelium to give novel dendritic-like cells
نویسندگان
چکیده
Hematopoietic cell lineages are best described in terms of distinct progenitors with limited differentiative capacity. To distinguish cell lineages, it is necessary to define progenitors and induce their differentiation in vitro. We previously reported in vitro development of immature dendritic-like cells (DCs) in long-term cultures (LTCs) of murine spleen, and in cocultures of spleen or bone marrow (BM) over splenic endothelial cell lines derived from LTCs. Cells produced are phenotypically distinct CD11bhiCD11cloCD8 MHCII cells, tentatively named L-DCs. Here we delineate L-DC progenitors as different from known DC progenitors in BM and DC precursors in spleen. The progenitor is contained within the lineage-negative (Lin) c-kit subset in neonatal and adult spleen. This subset has multipotential reconstituting ability in mice. In neonatal spleen, the progenitor is further enriched within the c-kitlo and CD34 subsets of Lin c-kit cells. These cells seed cocultures of splenic endothelial cells, differentiating to give L-DCs that can activate T cells. L-DC progenitors are distinguishable from described splenic CD11clo DC precursors and from Fms-like tyrosine kinase 3 DC progenitors in BM. Overall, this study confirms that LTCs are a physiologically relevant culture system for in vitro development of a novel DC type from spleen progenitors. (Blood. 2010; 115(18):3678-3685)
منابع مشابه
Development of Two Distinct Dendritic-Like APCs in the Context of Splenic Stroma
Murine splenic stroma has been found to provide an in vitro niche for hematopoiesis of dendritic-like APC. Two distinct cell types have been characterized. The novel "L-DC" subset has cross-presenting capacity, leading to activation of CD8(+) T cells, but not activating CD4(+) T cells, which is consistent with their CD11c(lo)CD11b(hi)MHC-II(-) phenotype. For L-DC, an equivalent tissue-specific ...
متن کاملInvestigation of murine spleen as a niche for hematopoiesis.
BACKGROUND Spleen as a lymphoid tissue is specialized for monitoring blood and mounting immunity against blood-borne antigens. Antigen-presenting cells present in spleen commonly develop from bone marrow-derived precursors that enter blood circulation. However, a distinct splenic myeloid antigen-presenting cell subset described in this laboratory, namely "dendritic-like cells" (L-DC), has been ...
متن کاملDistinct Progenitor Origin Distinguishes a Lineage of Dendritic-Like Cells in Spleen
The dendritic cell (DC) compartment comprises subsets of cells with distinct phenotypes. Previously this lab reported methodology for hematopoiesis of dendritic-like cells in vitro dependent on a murine splenic stromal cell line (5G3). Co-cultures of lineage-depleted bone marrow (Lin(-) BM) over 5G3 continuously produced a distinct population of dendritic-like "L-DC" for up to 35 days. Here the...
متن کاملDendritic cell development in long-term spleen stromal cultures.
The cellular microenvironments in which dendritic cells (DCs) develop are not known. DCs are commonly expanded from CD34+ bone marrow precursors or blood monocytes using a cocktail of growth factors including GM-CSF. However, cytokine-supported cultures are not suitable for studying the intermediate stages of DC development, since progenitors are quickly driven to become mature DCs that undergo...
متن کاملMolecular definition of an in vitro niche for dendritic cell development.
OBJECTIVE Although dendritic cell (DC) precursors have been isolated from many lymphoid sites, the regulation and location of early DC development is still poorly understood. Here we describe a splenic microenvironment that supports DC hematopoiesis in vitro and identify gene expression specific for that niche. METHODS The DC supportive function of the STX3 splenic stroma and the lymph node-d...
متن کامل