斯坦福大学医学院Charles K.F. Chan团队在研究中取得进展。他们报道了人类骨骼的发育和再生是由跨越骨骼部位的干细胞的功能多样性所决定的。相关论文于2025年3月20日发表在《细胞—干细胞》杂志上。

该课题组人员整合了人类骨骼干细胞（hSSCs）的前瞻性分离；CD45^-CD235a^-TIE2^-CD31^-CD146^-PDPN⁺CD73⁺CD164⁺)，通过功能分析和单细胞RNA测序（scRNA-seq）分析，鉴定hSSCs在发育过程中的软骨、成骨、间质和纤维化亚型及其与骨骼表型的联系。小组绘制了hSSCs亚型在多个骨骼部位的不同组成，并展示了它们独特的体内克隆动态。课题组研究人员发现与年龄相关的骨形成和再生障碍的变化源于hSSCs池的病理性成纤维细胞转移。利用布尔算法，研究组揭示了基因调控网络，决定了造血干细胞产生特定骨组织的能力差异。重要的是，hSSCs谱系动力学在药理学上是可延展性的，这为治疗异常的hSSCs多样性提供了一种新的策略，而异常的hSSCs多样性是衰老和骨骼疾病的核心。

研究人员表示，骨骼是人体结构和组成最多样化的器官系统之一，依赖于独特的细胞动力学。

附：英文原文

Title: Human skeletal development and regeneration are shaped by functional diversity of stem cells across skeletal sites

Author: Thomas H. Ambrosi, Sahar Taheri, Kun Chen, Rahul Sinha, Yuting Wang, Ethan J. Hunt, L. Henry Goodnough, Matthew P. Murphy, Holly M. Steininger, Malachia Y. Hoover, Franco Felix, Kelly C. Weldon, Lauren S. Koepke, Jan Sokol, Daniel Dan Liu, Liming Zhao, Stephanie D. Conley, Wan-Jin Lu, Maurizio Morri, Norma F. Neff, Noelle L. Van Rysselberghe, Erika E. Wheeler, Yongheng Wang, J. Kent Leach, Augustine Saiz, Aijun Wang, George P. Yang, Stuart Goodman, Julius A. Bishop, Michael J. Gardner, Derrick C. Wan, Irving L. Weissman, Michael T. Longaker, Debashis Sahoo, Charles K.F. Chan

Issue&Volume: 2025-03-20

Abstract: The skeleton is one of the most structurally and compositionally diverse organ systems in the human body, depending on unique cellular dynamisms. Here, we integrate prospective isolation of human skeletal stem cells (hSSCs; CD45CD235aTIE2CD31CD146PDPN+CD73+CD164+) from ten skeletal sites with functional assays and single-cell RNA sequencing (scRNA-seq) analysis to identify chondrogenic, osteogenic, stromal, and fibrogenic subtypes of hSSCs during development and their linkage to skeletal phenotypes. We map the distinct composition of hSSC subtypes across multiple skeletal sites and demonstrate their unique in vivo clonal dynamics. We find that age-related changes in bone formation and regeneration disorders stem from a pathological fibroblastic shift in the hSSC pool. Utilizing a Boolean algorithm, we uncover gene regulatory networks that dictate differences in the ability of hSSCs to generate specific skeletal tissues. Importantly, hSSC lineage dynamics are pharmacologically malleable, providing a new strategy to treat aberrant hSSC diversity central to aging and skeletal maladies.

DOI: 10.1016/j.stem.2025.02.013

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00081-5