Aging and obesity induce ectopic adipocyte accumulation in bone marrow cavities. This process is thought to impair osteogenic and hematopoietic regeneration. Here we specify the cellular identities of the adipogenic and osteogenic lineages of the bone. While aging impairs the osteogenic lineage, high-fat diet feeding activates expansion of the adipogenic lineage, an effect that is significantly enhanced in aged animals. We further describe a mesenchymal sub-population with stem cell-like characteristics that gives rise to both lineages and, at the same time, acts as a principal component of the hematopoietic niche by promoting competitive repopulation following lethal irradiation. Conversely, bone-resident cells committed to the adipocytic lineage inhibit hematopoiesis and bone healing, potentially by producing excessive amounts of Dipeptidyl peptidase-4, a protease that is a target of diabetes therapies. These studies delineate the molecular identity of the bone-resident adipocytic lineage, and they establish its involvement in age-dependent dysfunction of bone and hematopoietic regeneration.

中文翻译：

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肥胖和衰老过程中骨髓中的脂肪细胞蓄积会损害基于干细胞的造血和骨骼再生

衰老和肥胖会诱导异位脂肪细胞在骨髓腔中积累。认为该过程损害成骨和造血再生。在这里，我们指定骨骼的成脂和成骨血统的细胞身份。衰老会损害成骨细胞系，而高脂饮食喂养会促进成脂细胞系的扩展，这种作用在衰老动物中得到了显着增强。我们进一步描述了具有干细胞样特征的间充质亚群，该亚群引起了两个谱系，同时，通过促进致死性辐射后的竞争性再繁殖而成为造血生境的主要组成部分。相反，致力于脂肪细胞谱系的骨驻留细胞会抑制造血作用和骨骼愈合，可能会产生过量的二肽基肽酶4（Dipeptidyl peptidase-4），这是糖尿病治疗的靶标。这些研究勾勒出了常驻骨骼脂肪细胞谱系的分子特征，并建立了其与年龄相关的骨骼功能障碍和造血细胞再生的关系。