Cellular plasticity of the bone marrow niche promotes hematopoietic stem cell regeneration.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Hematopoietic stem cells (HSCs) regenerate after myeloablation, a procedure that adversely disrupts the bone marrow and drives leptin receptor-expressing cells, a key niche component, to differentiate extensively into adipocytes. Regeneration of the bone marrow niche is associated with the resolution of adipocytes, but the mechanisms remain poorly understood. Using Plin1-creER knock-in mice, we followed the fate of adipocytes in the regenerating niche in vivo. We found that bone marrow adipocytes were highly dynamic and dedifferentiated to leptin receptor-expressing cells during regeneration after myeloablation. Bone marrow adipocytes could give rise to osteolineage cells after skeletal injury. The cellular fate of steady-state bone marrow adipocytes was also plastic. Deletion of adipose triglyceride lipase (Atgl) from bone marrow stromal cells, including adipocytes, obstructed adipocyte dedifferentiation and led to severely compromised regeneration of HSCs as well as impaired B lymphopoiesis after myeloablation, but not in the steady state. Thus, the regeneration of HSCs and their niche depends on the cellular plasticity of bone marrow adipocytes.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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