Resting zone of the growth plate houses a unique class of skeletal stem cells.
Resting zone of the growth plate houses a unique class of skeletal stem cells.
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DOI：
10.1038/s41586-018-0662-5
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发表时间：
2018-11
期刊：
影响因子：
64.8
通讯作者：
Ono N
中科院分区：
文献类型：
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作者：
Mizuhashi K;Ono W;Matsushita Y;Sakagami N;Takahashi A;Saunders TL;Nagasawa T;Kronenberg HM;Ono N
骨骼干细胞通过产生多种细胞类型（包括软骨细胞、成骨细胞和骨髓基质细胞）来调节骨骼生长和体内平衡。新出现的模型假设一种独特类型的骨骼干细胞与生长板密切相关，生长板是一种特殊的软骨组织，在骨伸长中发挥着关键作用。休息区通过表达甲状旁腺激素相关蛋白（PTHrP）来维持生长板，该蛋白与肥大区释放的印度刺猬蛋白（Ihh）相互作用，同时提供其他软骨细胞的来源。然而，骨骼干细胞的身份以及它们如何在生长板中维持尚不清楚。在这里，我们发现骨骼干细胞是在出生后生长板静止区内的 PTHrP+ 软骨细胞中形成的。 PTHrP+ 软骨细胞表达一组骨骼干/祖细胞标记物，并且在培养条件下独特地具有骨骼干细胞的特性。细胞谱系分析显示，PTHrP+静息软骨细胞长期持续形成柱状软骨细胞，柱状软骨细胞肥大并成为生长板下方的成骨细胞和骨髓基质细胞。增殖区的转运放大软骨细胞由未分化细胞 (PTHrP) 的正向信号和肥大细胞 (Ihh) 的反向信号共同维持，为维持 PTHrP+ 静息软骨细胞的细胞命运提供了指导性线索。我们的研究结果揭示了一种独特的成体干细胞类型，它最初是单能的，在有丝分裂后阶段获得多能性，强调了骨骼细胞谱系的可塑性。该系统提供了一个模型，其中功能专用的干细胞及其生态位在出生后被指定，并通过严格的反馈调节系统在整个组织生长过程中维持。
Skeletal stem cells regulate bone growth and homeostasis by generating diverse cell types including chondrocytes, osteoblasts and marrow stromal cells. The emerging model postulates a distinct type of skeletal stem cells closely associated with the growth plate, a special cartilaginous tissue playing critical roles in bone elongation. The resting zone maintains the growth plate by expressing parathyroid hormone-related protein (PTHrP) that interacts with Indian hedgehog (Ihh) released from the hypertrophic zone, while providing a source of other chondrocytes. However, the identity of skeletal stem cells and how they are maintained in the growth plate are unknown. Here we show that skeletal stem cells are formed among PTHrP+ chondrocytes within the resting zone of the postnatal growth plate. PTHrP+ chondrocytes expressed a panel of markers for skeletal stem/progenitor cells and uniquely possessed the properties as skeletal stem cells in cultured conditions. Cell lineage analysis revealed that PTHrP+ resting chondrocytes continued to form columnar chondrocytes long term, which underwent hypertrophy and became osteoblasts and marrow stromal cells beneath the growth plate. Transit-amplifying chondrocytes in the proliferating zone, which was concertedly maintained by a forward signal from undifferentiated cells (PTHrP) and a reverse signal from hypertrophic cells (Ihh), provided instructive cues to maintain cell fates of PTHrP+ resting chondrocytes. Our findings unravel a unique somatic stem cell type that is initially unipotent and acquires multipotency at the post-mitotic stage, underscoring the malleable nature of the skeletal cell lineage. This system provides a model in which functionally dedicated stem cells and their niche are specified postnatally and maintained throughout tissue growth by a tight feedback regulation system.
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影响因子：
64.8
作者：
Busch, Katrin;Klapproth, Kay;Rodewald, Hans-Reimer
通讯作者：
Rodewald, Hans-Reimer
影响因子：
4.6
作者：
Mak, Kinglun Kingston;Kronenberg, Henry M.;Yang, Yingzi
通讯作者：
Yang, Yingzi
影响因子：
4.8
作者：
Abad, V;Meyers, JL;Baron, J
通讯作者：
Baron, J
影响因子：
64.8
作者：
Pardo-Saganta A;Tata PR;Law BM;Saez B;Chow RD;Prabhu M;Gridley T;Rajagopal J
通讯作者：
Rajagopal J
影响因子：
21.3
作者：
通讯作者：
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