Osteomacs interact with megakaryocytes and osteoblasts to regulate murine hematopoietic stem cell function

Area of Science:

• Hematology
• Stem Cell Biology
• Bone Biology

Background:

• Hematopoietic stem cell (HSC) function relies on interactions within the hematopoietic niche.
• Osteomacs (OMs) are cells residing in the calvaria (skull bone) and play a role in HSC maintenance.
• Distinguishing OMs from bone marrow (BM)-derived macrophages is crucial for understanding their specific functions.

Purpose of the Study:

• To characterize calvariae-resident osteomacs (OMs) and their interactions with megakaryocytes.
• To determine the role of OMs in supporting HSC function in conjunction with osteoblasts.
• To identify unique properties of OMs compared to BM-derived macrophages.

Main Methods:

• Neonatal calvarial cells were cultured with megakaryocytes.
• In vitro cultures containing osteoblasts, OMs, and megakaryocytes were used for serial transplantation assays.
• Nine-color flow cytometry was employed to analyze cell surface markers of OMs and BM-derived macrophages.

Main Results:

• Megakaryocytes significantly increased OM proliferation and augmented the HSC-enhancing activity of osteoblasts.
• HSC repopulating potential was best maintained in cultures with osteoblasts, OMs, and megakaryocytes.
• OMs exhibited unique cell surface marker expression (M-CSFR and CD166) compared to BM-derived macrophages, despite sharing other markers.

Conclusions:

• Calvariae-resident osteomacs (OMs) are essential for supporting HSC function.
• Megakaryocytes play a critical role in augmenting the synergistic activity of osteoblasts and OMs for HSC support.
• A novel network involving crosstalk between OMs, osteoblasts, and megakaryocytes is established as crucial for maintaining HSC function.