A vertebral skeletal stem cell lineage driving metastasis

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 and Matthew B. Greenblatt ()
Additional contact information
Jun Sun: Weill Cornell Medicine
Lingling Hu: Weill Cornell Medicine
Seoyeon Bok: Weill Cornell Medicine
Alisha R. Yallowitz: Weill Cornell Medicine
Michelle Cung: Weill Cornell Medicine
Jason McCormick: Weill Cornell Medicine
Ling J. Zheng: Weill Cornell Medicine
Shawon Debnath: Weill Cornell Medicine
Yuzhe Niu: Weill Cornell Medicine
Adrian Y. Tan: Weill Cornell Medicine
Sarfaraz Lalani: Weill Cornell Medicine
Kyle W. Morse: Hospital for Special Surgery
Daniel Shinn: Hospital for Special Surgery
Anthony Pajak: Hospital for Special Surgery
Mohammed Hammad: Research Division, Hospital for Special Surgery
Vincentius Jeremy Suhardi: Research Division, Hospital for Special Surgery
Zan Li: Weill Cornell Medicine
Na Li: Xiamen University
Lijun Wang: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Weiguo Zou: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Vivek Mittal: Weill Cornell Medicine
Mathias P. G. Bostrom: Research Division, Hospital for Special Surgery
Ren Xu: Xiamen University
Sravisht Iyer: Hospital for Special Surgery
Matthew B. Greenblatt: Weill Cornell Medicine

Nature, 2023, vol. 621, issue 7979, 602-609

Abstract: 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.

Date: 2023
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-023-06519-1 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:621:y:2023:i:7979:d:10.1038_s41586-023-06519-1

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-023-06519-1

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().