Cellular heterogeneity of human fallopian tubes in normal and hydrosalpinx disease states identified using scRNA-seq
Ulrich ND, Shen YC, Ma Q, Yang K, Hannum DF, Jones A, Machlin J, Randolph JF Jr, Smith YR, Schon SB, Shikanov A, Marsh EE, Lieberman R, Gurczynski SJ, Moore BB, Li JZ, Hammoud S. Cellular heterogeneity of human fallopian tubes in normal and hydrosalpinx disease states identified using scRNA-seq. Dev Cell. 2022 Apr 11;57(7):914-929.e7. doi: 10.1016/j.devcel.2022.02.017. Epub 2022 Mar 22. PMID: 35320732; PMCID: PMC9007916.
The fallopian tube contains epithelial cells, stromal cells and immune cells. This study makes an atlas of these cell types and subtypes in normal and diseased conditions. They find four ciliated and six non-ciliated secretory cells. According to their analysis, two of the secretory subtypes represent potential progenitors of secretory, ciliated and stromal cells.
Secretory cells are marked by PAX8+/KRT7+, ciliated cells by FOXJ1+/CAPS+ and peg cells by EPCAM+/CD44+/ITGA6+. These peg cells can generate ciliated and secretory cells in vitro which led to them being considered progenitor cells. Their decrease was associated with a decrease in ovarian cancer risk suggesting that peg cells were the cell of origin for HGSOC.
Interestingly, as an example of transcriptional heterogeneity, one of the ciliated cell subtypes, CE1-3 was a transitional population that had the markers of both ciliated and secretory cells. They also observed transcriptomic differences across the anatomic segments they studied. Gene expression values showed some differences for each cell type in each of the FT segments. Genes may be dynamically regulated to achieve normal reproduction or in response to disease.
They found two groups of progenitor cells, both secretory subtypes. One were the precursors of mature secretory cells and the others had a bifurcating trajectory leading to either ciliated cells or stromal cells.
They address a paper that identified two transitional populations with pseudotime. One of these was purported to be a RUNX3+ progenitor population, but the data from this study did not support it. RUNX3+ is a marker for T and natural killer cells and is not expressed highly in the other epithelial cells. The highest expression of RUNX3 in epithelial cells is in a secretory subtype that is not a predicted progenitor according to RNA velocity.