title: Identification of the Common Origins of Osteoclasts, Macrophages, and Dendritic Cells in Human Hematopoiesis.
abstract: 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)α(high) subset that constituted less than 0.5% of total BM. These IL3Rα(high) cells also generated macrophages (MΦs) and dendritic cells (DCs) but lacked granulocyte (GR)-differentiation potential, as demonstrated at the clonal level. The IL3Rα(low) subset was re-defined as common progenitor of GR, MΦ, OC, and DC (GMODP) and gave rise to the IL3Rα(high) subset that was identified as common progenitor of MΦ, OC, and DC (MODP). Unbiased transcriptome analysis of CD11b(-)CD34(+)c-KIT(+)FLT3(+) IL3Rα(low) and IL3Rα(high) subsets corroborated our definitions of the GMODP and MODP and their developmental relationship.
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam 1066 CX, the Netherlands. Electronic address: y.xiao@nki.nl.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam 1066 CX, the Netherlands.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Zijl
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam 1066 CX, the Netherlands.
authors.forename: Liqin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam 1066 CX, the Netherlands.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: de Groot
authors.affiliation: Division of Stem Cell Transplantation, Department of Pediatrics, Leiden University Medical Center, Leiden 2300 RC, the Netherlands.
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: van Tol
authors.affiliation: Division of Stem Cell Transplantation, Department of Pediatrics, Leiden University Medical Center, Leiden 2300 RC, the Netherlands.
authors.forename: Arjan C
authors.initials: AC
authors.lastname: Lankester
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam 1066 CX, the Netherlands. Electronic address: j.borst@nki.nl.
authors.forename: Jannie
authors.initials: J
authors.lastname: Borst
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D020869:Gene Expression Profiling; D006410:Hematopoiesis; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053650:Interleukin-3 Receptor alpha Subunit / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D008969:Molecular Sequence Data; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D017422:Sequence Analysis, DNA; D059467:Transcriptome; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D039481:CD11b Antigen; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit; D012333:RNA, Messenger; C497970:FLT3 protein, human; D019009:Proto-Oncogene Proteins c-kit; D051941:fms-Like Tyrosine Kinase 3