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Cellular plasticity of the bone marrow niche promotes hematopoietic stem cell regeneration
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Cellular plasticity of the bone marrow niche promotes hematopoietic stem cell regeneration
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Journal Article
Cellular plasticity of the bone marrow niche promotes hematopoietic stem cell regeneration
2023
Overview
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.
Mouse lineage tracing in regenerating bone marrow after myeloablation shows a dynamic dedifferentiation of mature adipocytes into bone marrow stromal cells. Lipolysis disruption obstructs adipocyte dedifferentiation and hematopoietic stem cell regeneration.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
