Osterix-Cre marks distinct subsets of CD45- and CD45+ stromal populations in extra-skeletal tumors with pro-tumorigenic characteristics
- Washington University in St Louis, United States
Abstract
Cancer-associated fibroblasts (CAFs) are a heterogeneous population of mesenchymal cells supporting tumor progression, whose origin remains to be fully elucidated. Osterix (Osx) is a marker of osteogenic differentiation, expressed in skeletal progenitor stem cells and bone-forming osteoblasts. We report Osx expression in CAFs and by using Osx-cre;TdTomato reporter mice we confirm the presence and pro-tumorigenic function of TdTOSX+ cells in extra-skeletal tumors. Surprisingly, only a minority of TdTOSX+ cells expresses fibroblast and osteogenic markers. The majority of TdTOSX+ cells express the hematopoietic marker CD45, have a genetic and phenotypic profile resembling that of tumor infiltrating myeloid and lymphoid populations, but with higher expression of lymphocytic immune suppressive genes. We find Osx transcript and Osx protein expression early during hematopoiesis, in subsets of hematopoietic stem cells and multipotent progenitor populations. Our results indicate that Osx marks distinct tumor promoting CD45- and CD45+ populations and challenge the dogma that Osx is expressed exclusively in cells of mesenchymal origin.
Data availability
Sequencing data are deposited in GEO under accession code GSE143586https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE143586
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GSE143586NCBI Gene Expression Omnibus, GSE143586.
Article and author information
Author details
Funding
National Institutes of Health (R01 CA235096)
- Roberta Faccio
National Institutes of Health (R01 AR066551)
- Roberta Faccio
Shriners Hospital (P19-07408CR)
- Roberta Faccio
Siteman Cancer Center
- Roberto Civitelli
- Roberta Faccio
JIT Award by Washinghton University Institute for Clinical and Translational Sciences (TR000448)
- Francesca Fontana
- Roberto Civitelli
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All the animals were handled according to the Institutional Animal Care and Use Committee (IACUC) protocols (#2016-0228 and # 2019-0982 to RF, #2014-0279 and #2017-0095 to RC).
Copyright
© 2020, Ricci et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Osterix-Cre marks distinct subsets of CD45- and CD45+ stromal populations in extra-skeletal tumors with pro-tumorigenic characteristics
eLife 9:e54659.
https://doi.org/10.7554/eLife.54659
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