TY - JOUR
T1 - A vertebral skeletal stem cell lineage driving metastasis
AU - Sun, Jun
AU - Hu, Lingling
AU - Bok, Seoyeon
AU - Yallowitz, Alisha R.
AU - Cung, Michelle
AU - McCormick, Jason
AU - Zheng, Ling J.
AU - Debnath, Shawon
AU - Niu, Yuzhe
AU - Tan, Adrian Y.
AU - Lalani, Sarfaraz
AU - Morse, Kyle W.
AU - Shinn, Daniel
AU - Pajak, Anthony
AU - Hammad, Mohammed
AU - Suhardi, Vincentius Jeremy
AU - Li, Zan
AU - Li, Na
AU - Wang, Lijun
AU - Zou, Weiguo
AU - Mittal, Vivek
AU - Bostrom, Mathias P.G.
AU - Xu, Ren
AU - Iyer, Sravisht
AU - Greenblatt, Matthew B.
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023/9/21
Y1 - 2023/9/21
N2 - Vertebral bone is subject to a distinct set of disease processes from long bones, including a much higher rate of solid tumour metastases 1–4. 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.
AB - Vertebral bone is subject to a distinct set of disease processes from long bones, including a much higher rate of solid tumour metastases 1–4. 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.
UR - http://www.scopus.com/inward/record.url?scp=85171306709&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85171306709&partnerID=8YFLogxK
U2 - 10.1038/s41586-023-06519-1
DO - 10.1038/s41586-023-06519-1
M3 - Article
C2 - 37704733
AN - SCOPUS:85171306709
SN - 0028-0836
VL - 621
SP - 602
EP - 609
JO - Nature
JF - Nature
IS - 7979
ER -