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Identification of the Common Origins of Osteoclasts, Macrophages, and Dendritic Cells in Human Hematopoiesis.

Xiao Y, Zijl S, Wang L, de Groot DC, van Tol MJ, Lankester AC, Borst J - Stem Cell Reports (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Immunology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam 1066 CX, the Netherlands. Electronic address: y.xiao@nki.nl.

No MeSH data available.


Related in: MedlinePlus

Identification of OC Progenitors in Human BM(A) Proposed models of hematopoietic development, as based on Doulatov et al. (2012) (left) and Görgens et al. (2013) (right). OC origin is proposed by us.(B) Gating strategy for sorting of the live, CD11b− G1, G2a and b, and G3a and b populations from ficolled BM.(C) Light microscopic image showing TRAP+ multi-nuclear OC derived from the G2b population.(D) RT-PCR-based mRNA expression of the indicated genes defined in the FLT3− (G2a) and FLT3+ (G2b) subsets of CD11b−CD34+c-KIT+ BM cells.(E) Gating for sorting live (PI−), IL3Rαlow, and IL3Rαhigh CD11b−CD34+c-KIT+FLT3+ cells from ficolled BM and lineage marker analysis.(F) The contribution (%) of the subsets to the total number of live cells in ficolled BM (mean + SEM; seven donors).(G) Flow cytometric detection of the indicated markers on the IL3Rαlow and IL3Rαhigh subsets (Ctrl, unstained IL3Rαlow samples), representative of three donors.(H and I) OC differentiation of IL3Rαlow and IL3Rαhigh subsets was analyzed at days 7–9. (H) OC differentiation was quantified as number (#) per well of (left) all TRAP+ cells and (right) TRAP+ cells with more than three nuclei (mean + SEM; five donors; ∗∗∗p < 0.001). (I) The phenotypic appearance of TRAP-stained OC cultures was determined by CCD microscopy. Green, DAPI staining of nuclei; gray/black, TRAP staining.See also Figure S1.
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fig1: Identification of OC Progenitors in Human BM(A) Proposed models of hematopoietic development, as based on Doulatov et al. (2012) (left) and Görgens et al. (2013) (right). OC origin is proposed by us.(B) Gating strategy for sorting of the live, CD11b− G1, G2a and b, and G3a and b populations from ficolled BM.(C) Light microscopic image showing TRAP+ multi-nuclear OC derived from the G2b population.(D) RT-PCR-based mRNA expression of the indicated genes defined in the FLT3− (G2a) and FLT3+ (G2b) subsets of CD11b−CD34+c-KIT+ BM cells.(E) Gating for sorting live (PI−), IL3Rαlow, and IL3Rαhigh CD11b−CD34+c-KIT+FLT3+ cells from ficolled BM and lineage marker analysis.(F) The contribution (%) of the subsets to the total number of live cells in ficolled BM (mean + SEM; seven donors).(G) Flow cytometric detection of the indicated markers on the IL3Rαlow and IL3Rαhigh subsets (Ctrl, unstained IL3Rαlow samples), representative of three donors.(H and I) OC differentiation of IL3Rαlow and IL3Rαhigh subsets was analyzed at days 7–9. (H) OC differentiation was quantified as number (#) per well of (left) all TRAP+ cells and (right) TRAP+ cells with more than three nuclei (mean + SEM; five donors; ∗∗∗p < 0.001). (I) The phenotypic appearance of TRAP-stained OC cultures was determined by CCD microscopy. Green, DAPI staining of nuclei; gray/black, TRAP staining.See also Figure S1.

Mentions: The hematopoietic tree describes the developmental pathways of all blood cells emanating from the pluripotent hematopoietic stem cell (HSC). The self-renewing HSC yields the multipotent progenitor (MPP), which in turn gives rise to more lineage-restricted, oligopotent precursors. The classical model dictates that the MPP bifurcates into a common myeloid progenitor (CMP) and a common lymphoid progenitor (CLP). The CMP in turn would bifurcate into the megakaryocyte/erythrocyte progenitor (MEP) and the granulocyte (GR)/MΦ progenitor (GMP). GRs, monocytes/MΦs, and DCs were thought to arise downstream of the GMP (Weissman and Shizuru, 2008). However, in an alternative model based on mouse data, the MPP bifurcates into a precursor with megakaryocyte/erythroid potential and one with combined myeloid and lymphoid potential (Kawamoto et al., 2010). This myeloid-based model was supported by the identification of a murine lympho/myeloid precursor (LMPP) devoid of megakaryocyte/erythroid potential (Adolfsson et al., 2005). Also in line with the myeloid-based model was the identification of a human multilymphoid progenitor (MLP) that gave rise to lymphoid cells, MΦs, and DCs (Doulatov et al., 2010). This MLP replaced the CLP in the scheme of human hematopoiesis (Doulatov et al., 2012). In the proposed scenario, both MLP and GMP can yield MΦs and DCs, whereas the GMP can additionally give rise to GRs (Figure 1A). Findings in humans also supported the existence of the LMPP (Goardon et al., 2011) and suggested that it bifurcates into the MLP and the GMP (Görgens et al., 2013; Figure 1A). Recent data in human also revise the view on the CMP, in accordance to findings in the mouse (Kawamoto et al., 2010): the human MPP was found to yield a common erythro-myeloid progenitor (EMP) that gives rise to the MEP and to a precursor of eosinophilic and basophilic GRs (EoBP) (Mori et al., 2009; Görgens et al., 2013). In the revised scheme, the CMP is absent and the GMP lies downstream of the LMPP (Figure 1A).


Identification of the Common Origins of Osteoclasts, Macrophages, and Dendritic Cells in Human Hematopoiesis.

Xiao Y, Zijl S, Wang L, de Groot DC, van Tol MJ, Lankester AC, Borst J - Stem Cell Reports (2015)

Identification of OC Progenitors in Human BM(A) Proposed models of hematopoietic development, as based on Doulatov et al. (2012) (left) and Görgens et al. (2013) (right). OC origin is proposed by us.(B) Gating strategy for sorting of the live, CD11b− G1, G2a and b, and G3a and b populations from ficolled BM.(C) Light microscopic image showing TRAP+ multi-nuclear OC derived from the G2b population.(D) RT-PCR-based mRNA expression of the indicated genes defined in the FLT3− (G2a) and FLT3+ (G2b) subsets of CD11b−CD34+c-KIT+ BM cells.(E) Gating for sorting live (PI−), IL3Rαlow, and IL3Rαhigh CD11b−CD34+c-KIT+FLT3+ cells from ficolled BM and lineage marker analysis.(F) The contribution (%) of the subsets to the total number of live cells in ficolled BM (mean + SEM; seven donors).(G) Flow cytometric detection of the indicated markers on the IL3Rαlow and IL3Rαhigh subsets (Ctrl, unstained IL3Rαlow samples), representative of three donors.(H and I) OC differentiation of IL3Rαlow and IL3Rαhigh subsets was analyzed at days 7–9. (H) OC differentiation was quantified as number (#) per well of (left) all TRAP+ cells and (right) TRAP+ cells with more than three nuclei (mean + SEM; five donors; ∗∗∗p < 0.001). (I) The phenotypic appearance of TRAP-stained OC cultures was determined by CCD microscopy. Green, DAPI staining of nuclei; gray/black, TRAP staining.See also Figure S1.
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fig1: Identification of OC Progenitors in Human BM(A) Proposed models of hematopoietic development, as based on Doulatov et al. (2012) (left) and Görgens et al. (2013) (right). OC origin is proposed by us.(B) Gating strategy for sorting of the live, CD11b− G1, G2a and b, and G3a and b populations from ficolled BM.(C) Light microscopic image showing TRAP+ multi-nuclear OC derived from the G2b population.(D) RT-PCR-based mRNA expression of the indicated genes defined in the FLT3− (G2a) and FLT3+ (G2b) subsets of CD11b−CD34+c-KIT+ BM cells.(E) Gating for sorting live (PI−), IL3Rαlow, and IL3Rαhigh CD11b−CD34+c-KIT+FLT3+ cells from ficolled BM and lineage marker analysis.(F) The contribution (%) of the subsets to the total number of live cells in ficolled BM (mean + SEM; seven donors).(G) Flow cytometric detection of the indicated markers on the IL3Rαlow and IL3Rαhigh subsets (Ctrl, unstained IL3Rαlow samples), representative of three donors.(H and I) OC differentiation of IL3Rαlow and IL3Rαhigh subsets was analyzed at days 7–9. (H) OC differentiation was quantified as number (#) per well of (left) all TRAP+ cells and (right) TRAP+ cells with more than three nuclei (mean + SEM; five donors; ∗∗∗p < 0.001). (I) The phenotypic appearance of TRAP-stained OC cultures was determined by CCD microscopy. Green, DAPI staining of nuclei; gray/black, TRAP staining.See also Figure S1.
Mentions: The hematopoietic tree describes the developmental pathways of all blood cells emanating from the pluripotent hematopoietic stem cell (HSC). The self-renewing HSC yields the multipotent progenitor (MPP), which in turn gives rise to more lineage-restricted, oligopotent precursors. The classical model dictates that the MPP bifurcates into a common myeloid progenitor (CMP) and a common lymphoid progenitor (CLP). The CMP in turn would bifurcate into the megakaryocyte/erythrocyte progenitor (MEP) and the granulocyte (GR)/MΦ progenitor (GMP). GRs, monocytes/MΦs, and DCs were thought to arise downstream of the GMP (Weissman and Shizuru, 2008). However, in an alternative model based on mouse data, the MPP bifurcates into a precursor with megakaryocyte/erythroid potential and one with combined myeloid and lymphoid potential (Kawamoto et al., 2010). This myeloid-based model was supported by the identification of a murine lympho/myeloid precursor (LMPP) devoid of megakaryocyte/erythroid potential (Adolfsson et al., 2005). Also in line with the myeloid-based model was the identification of a human multilymphoid progenitor (MLP) that gave rise to lymphoid cells, MΦs, and DCs (Doulatov et al., 2010). This MLP replaced the CLP in the scheme of human hematopoiesis (Doulatov et al., 2012). In the proposed scenario, both MLP and GMP can yield MΦs and DCs, whereas the GMP can additionally give rise to GRs (Figure 1A). Findings in humans also supported the existence of the LMPP (Goardon et al., 2011) and suggested that it bifurcates into the MLP and the GMP (Görgens et al., 2013; Figure 1A). Recent data in human also revise the view on the CMP, in accordance to findings in the mouse (Kawamoto et al., 2010): the human MPP was found to yield a common erythro-myeloid progenitor (EMP) that gives rise to the MEP and to a precursor of eosinophilic and basophilic GRs (EoBP) (Mori et al., 2009; Görgens et al., 2013). In the revised scheme, the CMP is absent and the GMP lies downstream of the LMPP (Figure 1A).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Immunology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam 1066 CX, the Netherlands. Electronic address: y.xiao@nki.nl.

No MeSH data available.


Related in: MedlinePlus