The Repertoire of Serous Ovarian Cancer Non-genetic Heterogeneity Revealed by Single-Cell Sequencing of Normal Fallopian Tube Epithelial Cells
Hu Z, Artibani M, Alsaadi A, Wietek N, Morotti M, Shi T, Zhong Z, Santana Gonzalez L, El-Sahhar S, Carrami EM, Mallett G, Feng Y, Masuda K, Zheng Y, Chong K, Damato S, Dhar S, Campo L, Garruto Campanile R, Soleymani Majd H, Rai V, Maldonado-Perez D, Jones S, Cerundolo V, Sauka-Spengler T, Yau C, Ahmed AA. The Repertoire of Serous Ovarian Cancer Non-genetic Heterogeneity Revealed by Single-Cell Sequencing of Normal Fallopian Tube Epithelial Cells. Cancer Cell. 2020 Feb 10;37(2):226-242.e7. doi: 10.1016/j.ccell.2020.01.003. PMID: 32049047.
Cancer cells with the same genetic background can have different phenotypic states that help them survive, invade, metastasize, and resist therapies. To understand their plasticity, it is important to identify their individual cell states or the cell states of their cell-of-origin since the cell-of-origin states may be recapitulated in the daughter cells. HGSOC cells are difficult to stratify and have transcriptomic heterogeneity. This work analyzed the cellular states present in HGSOC tumors.
They first found that overnight and long-term culture introduced changes in gene-expression that could introduce significant biases in the data. So they used fresh tissue and removed cells expressing FOS and JUN as part of a stress reponse from sample preparation.
In the cleaned dataset they identified five cell states: EMT, cell cycle, differentiated, KRT17, and ciliated. The EMT population expressed KRT7 and EPCAM and EMT score was associated with poor survival independently of other factors and had a high sensitivity in identifying poor prognoses. They also found a population that expressed both a secretory marker KRT7 and a ciliated marker CAPS. This population was thought to represent an intermediate between secretory and ciliated cell types.
Using the five identified subtypes, they took bulk RNA-seq data and deconvolved the cell populations. The ciliated tumor subtype was highly enriched in low-grade HGSOC which suggested to them that the grades of of SOC are associated with their ability to differentiate into cells that look like ciliated cells. Or the enrichment of ciliated markers is a distinguishing feature of low-grade tumors.