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

Xiao, Yanling; Zijl, Sebastiaan; Wang, Liqin; Groot, Daniel C. de; Tol, Maarten J. van; Lankester, Arjan C.; Borst, Jannie

doi:10.1016/j.stemcr.2015.04.012

Cited by 43 publications

(57 citation statements)

References 28 publications

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“…We found that the GMP population could give rise to OCs (supplemental Figure 1E). This result, together with our findings in humans, 15 supports the concept that the GMP population contains a progenitor with combined GR, MF, OC, and DC potential that lies upstream of the MODP. We further hypothesized that the MOP lies downstream of the MODP ( Figure 1A).…”

Section: Cell Surface Markers Of Modp and Mopsupporting

confidence: 89%

“…We recently described the human (h)MODP 15 and noted that its cell surface phenotype was similar to that of the hCDP that was described shortly before that 28 ( Figure 7H). Both progenitor populations are very rare, representing about 0.2% of total BM ( Figure 7I).…”

Section: Comparison Of Cdp and Mdp With Modp And Mop: Differentiationmentioning

confidence: 56%

“…35 DC output from the murine MODP was similar upon culture with Flt3L alone or in combination with low-dose M-CSF (supplemental Figure 3A-B), whereas DC output from the human MODP was increased by the combination. 15 Strikingly, the murine MODP preferentially generated F4/ 80 1 CD11b 1 MFs when cultured with Flt3L and high-dose M-CSF (supplemental Figure 3C). So the dose of M-CSF was important for the developmental fate of the MODP offspring.…”

Section: Validation Of Developmental Potential Of Modp and Mop: Formamentioning

confidence: 95%

“…15 For OC differentiation, cells were cultured in a-MEM with 10% FCS, 25 ng/mL recombinant human (rh) M-CSF, and 40 ng/mL rh RANKL. For MF differentiation, cells were cultured on a monolayer of OP9 cells in IMDM with 10% FCS, 25 ng/mL rh M-CSF, and 1000 U/mL rh interleukin-6 (IL-6).…”

Section: In Vitro Differentiation Of Human Progenitors Into Ocs or Mfsmentioning

confidence: 99%

“…14 We have recently shown that the human GMP has combined GR, MF, OC, and DC potential and is thus a GMODP. We have also identified downstream of the human GMODP a tripotent MF/OC/DC progenitor (MODP) that is devoid of GR potential 15 ( Figure 1A). In the mouse, combined MF and OC potential has been identified in a B220 …”

Section: Introductionmentioning

confidence: 99%

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Macrophages and osteoclasts stem from a bipotent progenitor downstream of a macrophage/osteoclast/dendritic cell progenitor

Xiao¹,

Palomero²,

Grabowska³

et al. 2017

Blood Advances

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Key Points• Under homeostatic conditions, MFs, OCs, and DCs develop from a tripotent progenitor, the MODP.• (CDP) has been described as committed to plasmacytoid and conventional DC development.However, the human CDP proved identical to the MODP population, whereas the mouse CDP largely overlapped with the MODP population and was accordingly oligopotent for MF, OC, and DC development. The CX 3 CR1 1 MF/DC progenitor (MDP) population described in the mouse generated MFs and OCs but not DCs. Thus, monocytes/MFs, OCs, and DCs share a common progenitor that gives rise to a bipotent MF/OC progenitor, but a dedicated DC progenitor is currently undefined. The definition of these progenitor populations may serve diagnostics and interventions in diseases with pathogenic activity of MFs, OCs, or DCs.

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Section: Cell Surface Markers Of Modp and Mopsupporting

confidence: 89%

Section: Comparison Of Cdp and Mdp With Modp And Mop: Differentiationmentioning

confidence: 56%

Section: Validation Of Developmental Potential Of Modp and Mop: Formamentioning

confidence: 95%

Section: In Vitro Differentiation Of Human Progenitors Into Ocs or Mfsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Macrophages and osteoclasts stem from a bipotent progenitor downstream of a macrophage/osteoclast/dendritic cell progenitor

Xiao¹,

Palomero²,

Grabowska³

et al. 2017

Blood Advances

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Osteoclast precursors do not express CD68: results from CD68 promoter‐driven RANK transgenic mice

2017

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Macrophages and osteoclasts are thought to derive from CD68 lineage marker-positive common myeloid precursors. We used the CD68 promoter to drive an inducible receptor activator of NF-κB (iRANK) construct that selectively activates RANK signaling in myeloid cells in vivo. The cytoplasmic portion of RANK was fused to a mutant FK506 binding domain, which selectively binds the chemical inducer of dimerization AP20187 and initiates signaling. iRANK mRNA was expressed in macrophages isolated from peritoneal cavity, spleen and bone marrow-derived myeloid cells. Unexpectedly, AP20187 did not induce osteoclast formation in spleen and bone marrow-derived myeloid cells. However, AP20187-dependent RANK signaling induced ERK1/2 phosphorylation and mRNA expression of MMP9 and CathepsinK in peritoneal macrophages. Importantly, CD68 was not expressed until day 3 and day 5 in bone marrow and spleen myeloid cells, respectively. Contrary to dogma, osteoclast precursors do not express the lineage marker CD68.

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Pharmacological and biological therapeutic strategies for osteogenesis imperfecta

Marom¹,

Lee²,

Grafe³

et al. 2016

American J of Med Genetics Pt C

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Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by bone fragility, low bone mass, and bone deformities. The majority of cases are caused by autosomal dominant pathogenic variants in the COL1A1 and COL1A2 genes that encode type I collagen, the major component of the bone matrix. The remaining cases are caused by autosomal recessively or dominantly inherited mutations in genes that are involved in the post-translational modification of type I collagen, act as type I collagen chaperones, or are members of the signaling pathways that regulate bone homeostasis. The main goals of treatment in OI are to decrease fracture incidence, relieve bone pain, and promote mobility and growth. This requires a multi-disciplinary approach, utilizing pharmacological interventions, physical therapy, orthopedic surgery, and monitoring nutrition with appropriate calcium and vitamin D supplementation. Bisphosphonate therapy, which has become the mainstay of treatment in OI, has proven beneficial in increasing bone mass, and to some extent reducing fracture risk. However, the response to treatment is not as robust as is seen in osteoporosis, and it seems less effective in certain types of OI, and in adult OI patients as compared to most pediatric cases. New pharmacological treatments are currently being developed, including anti-resorptive agents, anabolic treatment, and gene- and cell-therapy approaches. These therapies are under different stages of investigation from the bench-side, to pre-clinical and clinical trials. In this review, we will summarize the recent findings regarding the pharmacological and biological strategies for the treatment of patients with OI. © 2016 Wiley Periodicals, Inc.

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

Cited by 43 publications

References 28 publications

Macrophages and osteoclasts stem from a bipotent progenitor downstream of a macrophage/osteoclast/dendritic cell progenitor

Macrophages and osteoclasts stem from a bipotent progenitor downstream of a macrophage/osteoclast/dendritic cell progenitor

Osteoclast precursors do not express CD68: results from CD68 promoter‐driven RANK transgenic mice

Pharmacological and biological therapeutic strategies for osteogenesis imperfecta

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