驱动转移的脊椎骨骼干细胞谱系。
A vertebral skeletal stem cell lineage driving metastasis.
发表日期:2023 Sep 13
作者:
Jun Sun, Lingling Hu, Seoyeon Bok, Alisha R Yallowitz, Michelle Cung, Jason McCormick, Ling J Zheng, Shawon Debnath, Yuzhe Niu, Adrian Y Tan, Sarfaraz Lalani, Kyle W Morse, Daniel Shinn, Anthony Pajak, Mohammed Hammad, Vincentius Jeremy Suhardi, Zan Li, Na Li, Lijun Wang, Weiguo Zou, Vivek Mittal, Mathias P G Bostrom, Ren Xu, Sravisht Iyer, Matthew B Greenblatt
来源:
Stem Cell Research & Therapy
摘要:
脊椎骨与长骨相比,受到一套不同的疾病过程影响,其中包括更高比率的实质性肿瘤转移1-4。迄今为止,脊椎骨的这种独特生物学基础仍然未知。在这里,我们确定了一个脊椎骨骨骼干细胞(vSSC),该细胞与ZIC1和PAX1共同表达,同时具有额外的细胞表面标志物。 vSSC显示出干性的正式证据,包括自我更新、标签保留,并位于其分化层次结构的顶点。 vSSC是脊椎骨形成的生理调节因子,因为阻断vSSC生成成骨细胞的能力会导致脊椎突和脊椎体的缺陷。vSSC的人类同源细胞可以在脊椎板细胞标本中被鉴定,并显示出保守的分化层次结构和干性特征。多方证据表明,vSSC对于乳腺癌观察到的高脊椎转移倾向具有贡献,部分原因是由于新型转移性营养因子MFGE8的分泌增加。总之,我们的结果表明,vSSC与其他骨骼干细胞有所不同,并介导脊椎的独特生理学和病理学,包括对高脊椎转移率的贡献。© 2023. 作者,专许给施普林格自然出版集团有限公司。
Vertebral bone is subject to a distinct set of disease processes from long bones, including a much higher rate of solid tumour metastases1-4. The basis for this distinct biology of vertebral bone has so far remained unknown. Here we identify a vertebral skeletal stem cell (vSSC) that co-expresses ZIC1 and PAX1 together with additional cell surface markers. vSSCs display formal evidence of stemness, including self-renewal, label retention and sitting at the apex of their differentiation hierarchy. vSSCs are physiologic mediators of vertebral bone formation, as genetic blockade of the ability of vSSCs to generate osteoblasts results in defects in the vertebral neural arch and body. Human counterparts of vSSCs can be identified in vertebral endplate specimens and display a conserved differentiation hierarchy and stemness features. Multiple lines of evidence indicate that vSSCs contribute to the high rates of vertebral metastatic tropism observed in breast cancer, owing in part to increased secretion of the novel metastatic trophic factor MFGE8. Together, our results indicate that vSSCs are distinct from other skeletal stem cells and mediate the unique physiology and pathology of vertebrae, including contributing to the high rate of vertebral metastasis.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.