Osteomacs interact with megakaryocytes and osteoblasts to regulate murine hematopoietic stem cell function
| Autor: | Joydeep Ghosh, Hao Wu, Linlin Xu, Evan R. Himes, Edward F. Srour, Marta B. Alvarez, Safa F. Mohamad, Jung Min Hong, Korbin M. Davis, Paul Childress, Angela Bruzzaniti, Irushi Abeysekera, Alexandra Aguilar-Perez, Melissa A. Kacena |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell type Chemistry Hematopoiesis and Stem Cells Hematopoietic stem cell Hematology Bone resorption Cell biology 03 medical and health sciences Haematopoiesis 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Multinucleate 030220 oncology & carcinogenesis medicine Bone marrow Stem cell Tartrate-resistant acid phosphatase |
| Zdroj: | Blood advances. 1(26) |
| ISSN: | 2473-9529 |
| Popis: | Networking between hematopoietic stem cells (HSCs) and cells of the hematopoietic niche is critical for stem cell function and maintenance of the stem cell pool. We characterized calvariae-resident osteomacs (OMs) and their interaction with megakaryocytes to sustain HSC function and identified distinguishing properties between OMs and bone marrow (BM)-derived macrophages. OMs, identified as CD45+F4/80+ cells, were easily detectable (3%-5%) in neonatal calvarial cells. Coculture of neonatal calvarial cells with megakaryocytes for 7 days increased OM three- to sixfold, demonstrating that megakaryocytes regulate OM proliferation. OMs were required for the hematopoiesis-enhancing activity of osteoblasts, and this activity was augmented by megakaryocytes. Serial transplantation demonstrated that HSC repopulating potential was best maintained by in vitro cultures containing osteoblasts, OMs, and megakaryocytes. With or without megakaryocytes, BM-derived macrophages were unable to functionally substitute for neonatal calvarial cell-associated OMs. In addition, OMs differentiated into multinucleated, tartrate resistant acid phosphatase-positive osteoclasts capable of bone resorption. Nine-color flow cytometric analysis revealed that although BM-derived macrophages and OMs share many cell surface phenotypic similarities (CD45, F4/80, CD68, CD11b, Mac2, and Gr-1), only a subgroup of OMs coexpressed M-CSFR and CD166, thus providing a unique profile for OMs. CD169 was expressed by both OMs and BM-derived macrophages and therefore was not a distinguishing marker between these 2 cell types. These results demonstrate that OMs support HSC function and illustrate that megakaryocytes significantly augment the synergistic activity of osteoblasts and OMs. Furthermore, this report establishes for the first time that the crosstalk between OMs, osteoblasts, and megakaryocytes is a novel network supporting HSC function. |
| Databáze: | OpenAIRE |
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