Myoepithelial progenitors as founder cells of hyperplastic human breast lesions upon PIK3CA transformation
Research output: Contribution to journal › Journal article › Research › peer-review
Documents
- Fulltext
Final published version, 3.13 MB, PDF document
The myoepithelial (MEP) lineage of human breast comprises bipotent and multipotent progenitors in ducts and terminal duct lobular units (TDLUs). We here assess whether this heterogeneity impacts on oncogenic PIK3CA transformation. Single cell RNA sequencing (scRNA-seq) and multicolor imaging reveal that terminal ducts represent the most enriched source of cells with ductal MEP markers including α-smooth muscle actin (α-SMA), keratin K14, K17 and CD200. Furthermore, we find neighboring CD200high and CD200low progenitors within terminal ducts. When sorted and kept in ground state conditions, their CD200low and CD200high phenotypes are preserved. Upon differentiation, progenitors remain multipotent and bipotent, respectively. Immortalized progenitors are transduced with mutant PIK3CA on an shp53 background. Upon transplantation, CD200low MEP progenitors distinguish from CD200high by the formation of multilayered structures with a hyperplastic inner layer of luminal epithelial cells. We suggest a model with spatially distributed MEP progenitors as founder cells of biphasic breast lesions with implications for early detection and prevention strategies.
Original language | English |
---|---|
Article number | 219 |
Journal | Communications Biology |
Volume | 5 |
Issue number | 1 |
Number of pages | 13 |
ISSN | 2399-3642 |
DOIs | |
Publication status | Published - 2022 |
Bibliographical note
Publisher Copyright:
© 2022, The Author(s).
Number of downloads are based on statistics from Google Scholar and www.ku.dk
ID: 301138743