Osterix-Cre marks distinct subsets of CD45- and CD45+ stromal populations in extra-skeletal tumors with pro-tumorigenic characteristics.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32755539.
- Also identified by DOI 10.7554/eLife.54659 and PMC identifier 7428306.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>Osx</i> expression in CAFs and by using Osx-cre;TdTomato reporter mice we confirm the presence and pro-tumorigenic function of TdT<sup>OSX</sup>+ cells in extra-skeletal tumors. Surprisingly, only a minority of TdT<sup>OSX</sup>+ cells expresses fibroblast and osteogenic markers. The majority of TdT<sup>OSX</sup>+ 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 <i>Osx</i> transcript and Osx protein expression early during hematopoiesis, in subsets of hematopoietic stem cells and multipotent progenitor populations. Our results indicate that <i>Osx</i> marks distinct tumor promoting CD45- and CD45+ populations and challenge the dogma that Osx is expressed exclusively in cells of mesenchymal origin.
Medical subject headings
- Cell Differentiation
- Leukocyte Common Antigens
- Neoplasms
- Osteoblasts
- Sp7 Transcription Factor
- Stem Cells