Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States.
Department of Orthopaedics, The First Hospital of China Medical University, Shenyang, China.
Elife. 2020 Apr 14;9:e54695. doi: 10.7554/eLife.54695.
Bone marrow mesenchymal lineage cells are a heterogeneous cell population involved in bone homeostasis and diseases such as osteoporosis. While it is long postulated that they originate from mesenchymal stem cells, the true identity of progenitors and their in vivo bifurcated differentiation routes into osteoblasts and adipocytes remain poorly understood. Here, by employing large scale single cell transcriptome analysis, we computationally defined mesenchymal progenitors at different stages and delineated their bi-lineage differentiation paths in young, adult and aging mice. One identified subpopulation is a unique cell type that expresses adipocyte markers but contains no lipid droplets. As non-proliferative precursors for adipocytes, they exist abundantly as pericytes and stromal cells that form a ubiquitous 3D network inside the marrow cavity. Functionally they play critical roles in maintaining marrow vasculature and suppressing bone formation. Therefore, we name them marrow adipogenic lineage precursors (MALPs) and conclude that they are a newly identified component of marrow adipose tissue.
骨髓间充质谱系细胞是一种异质性细胞群体,参与骨稳态和骨质疏松症等疾病。虽然长期以来一直假设它们来源于间充质干细胞,但真正的祖细胞的身份及其在体内分叉分化为成骨细胞和脂肪细胞的途径仍知之甚少。在这里,我们通过大规模单细胞转录组分析,在不同阶段计算定义了间充质祖细胞,并描绘了它们在年轻、成年和老年小鼠中的双谱系分化途径。一个被识别的亚群是一种独特的细胞类型,它表达脂肪细胞标记物,但不含脂滴。作为脂肪细胞的非增殖前体,它们大量存在于周细胞和基质细胞中,在骨髓腔内形成一个普遍存在的 3D 网络。它们在维持骨髓血管和抑制骨形成方面发挥着关键作用。因此,我们将它们命名为骨髓脂肪生成谱系前体细胞(MALPs),并得出结论,它们是骨髓脂肪组织的一个新发现的组成部分。