美国威尔康奈尔医学院Matthew B. Greenblatt研究组取得一项新突破。他们发现了可诱导转移的椎骨干细胞系。2023年9月13日出版的《自然》发表了这项成果。
研究人员鉴定了一种椎骨干细胞（vSSC），共同表达ZIC1和PAX等其他细胞表面标志物。vSSC具有典型的干细胞特性，包括自我更新、标签保留和处于其分化层次结构的顶点。vSSC是椎骨形成的生理介质，因为利用遗传方式破坏vSSC生产成骨细胞的能力会导致椎神经弓和身体缺陷。可在椎体标本中鉴定出人体对应的vSSC，并具有保守的分化层次结构和干细胞性特征。多种证据表明，vSSCs与乳腺癌中观察到的高椎体转移发生率有关，部分原因是由于新型转移营养因子MFGE8的分泌增加。
总之，该研究结果表明，vSSCs与其他骨骼干细胞不同，其介导椎骨的独特生理特性和病理学，例如导致椎骨转移率升高。
据悉，与长骨不同，椎骨与一系列疾病有关，也和更高的实体瘤转移率相关。到目前为止，造成脊椎骨这种独特生物特性的机制仍然未知。
附：英文原文
Title: A vertebral skeletal stem cell lineage driving metastasis
Author: Sun, Jun, Hu, Lingling, Bok, Seoyeon, Yallowitz, Alisha R., Cung, Michelle, McCormick, Jason, Zheng, Ling J., Debnath, Shawon, Niu, Yuzhe, Tan, Adrian Y., Lalani, Sarfaraz, Morse, Kyle W., Shinn, Daniel, Pajak, Anthony, Hammad, Mohammed, Suhardi, Vincentius Jeremy, Li, Zan, Li, Na, Wang, Lijun, Zou, Weiguo, Mittal, Vivek, Bostrom, Mathias P. G., Xu, Ren, Iyer, Sravisht, Greenblatt, Matthew B.
Issue&Volume: 2023-09-13
Abstract: 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. Vertebral osteoblasts in mouse and human are formed from a precursor skeletal stem cell population that is distinct from long bone skeletal stem cells in function, location and transcriptional programme.
DOI: 10.1038/s41586-023-06519-1
Source: https://www.nature.com/articles/s41586-023-06519-1
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
