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Identification of the Common Origins of Osteoclasts, Macrophages, and Dendritic Cells in Human Hematopoiesis #MMPMID26004632
Xiao Y; Zijl S; Wang L; de Groot D; van Tol M; Lankester A; Borst J
Stem Cell Reports 2015[Jun]; 4 (6): 984-94 PMID26004632show ga
Osteoclasts (OCs) originate from the myeloid cell lineage, but the successive steps in their lineage commitment are ill-defined, especially in humans. To clarify OC origin, we sorted cell populations from pediatric bone marrow (BM) by flow cytometry and assessed their differentiation potential in vitro. Within the CD11b?CD34+c-KIT+ BM cell population, OC-differentiation potential was restricted to FLT3+ cells and enriched in an IL3 receptor (R)?high subset that constituted less than 0.5% of total BM. These IL3R?high cells also generated macrophages (M?s) and dendritic cells (DCs) but lacked granulocyte (GR)-differentiation potential, as demonstrated at the clonal level. The IL3R?low subset was re-defined as common progenitor of GR, M?, OC, and DC (GMODP) and gave rise to the IL3R?high subset that was identified as common progenitor of M?, OC, and DC (MODP). Unbiased transcriptome analysis of CD11b?CD34+c-KIT+FLT3+ IL3R?low and IL3R?high subsets corroborated our definitions of the GMODP and MODP and their developmental relationship.