Postmenopausal Fallopian Tube and Ovary Atlas

A molecular atlas of the human postmenopausal fallopian tube and ovary (Lengyel et al., 2022), published in Cell Reports, maps the normal tissues in which high-grade serous ovarian cancer arises, after menopause, when most ovarian cancers are diagnosed. Using single-cell RNA and chromatin (ATAC) sequencing, the authors described what these tissues are made of, cell by cell, as a baseline against which disease can be compared.

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Key Findings

• Stromal cells dominate. The fallopian tube holds 11 major cell types and the ovary 6, and in both the most common is the stromal cell, which expresses aging-associated genes.
• Epithelial cells are a small minority of the tube. Secretory and ciliated cells, the cells from which high-grade serous cancer is thought to arise, make up about 8% of fallopian tube cells. The authors found that they express several ovarian cancer risk genes.
• Expression and chromatin agree. The two assays, run on different cells, describe the same cellular makeup, so the atlas can link each cell type's gene activity to its regulatory landscape.

The Atlas

• scRNA-seq: 86,708 cells; 60,574 from the fallopian tube (7 donors) and 26,134 from the ovary (6 donors).
• scATAC-seq: 59,118 cells; 40,803 from the fallopian tube (4 donors) and 18,315 from the ovary (3 donors).
• Source: the CZ CELLxGENE deposit of the paper; raw reads are held under controlled access at EGA.

Paper: Lengyel E, Li Y, Weigert M, et al. A molecular atlas of the human postmenopausal fallopian tube and ovary from single-cell RNA and ATAC sequencing. Cell Reports 41, 111838 (2022). doi:10.1016/j.celrep.2022.111838

Stromal Cells Make Up Most of Both Tissues

Stromal cells are 46% of fallopian tube cells and 83% of ovary cells. In these maps each dot is a cell, placed so that cells with similar gene expression sit together, and colored by cell type: the stromal population is the largest island in both tissues. Secretory and ciliated epithelial cells, together about 8% of the tube, form small clusters of their own, and the ovary has no epithelial population at all.

The Pattern Holds in Every Donor

The stromal majority is not driven by one or two samples: stromal cells are the largest group in every donor, in both tissues. Their share ranges from about a third to two thirds of each donor's fallopian tube cells, and from 60% to 98% of ovary cells.

Gene Expression and Chromatin Tell the Same Story

The authors profiled gene expression and chromatin accessibility in separate cells, partly from different donors. If both describe the same tissue, each cell type should make up a similar share of each assay. It does: each point is a cell type, and points fall close to the diagonal. That agreement is what lets the atlas connect a cell type's expressed genes to the regulatory regions behind them.

Each Cell Type Has a Distinct Identity

A panel of 24 well-known marker genes shows what sets each cell type apart: a marker is expressed strongly (dark color) and in many cells (big dot) in the cell types it defines. These identities are how the atlas places each cell, including the epithelial cells in which the authors found ovarian cancer risk genes expressed.

About These Charts

Cell counts reconcile with the paper for scRNA-seq (86,708). The deposited scATAC-seq data holds 59,118 cells, 712 fewer than the 59,830 in the paper's abstract.

RNA and ATAC labels come from different cells, so agreement is compared as fractions, not cell by cell. Pseudobulk values are per tissue and cell type means of the deposited expression matrix.

These charts were built in the Discovery Lab TRE from the CZ CELLxGENE deposit (TRE datasets ea8de879 and 880e8257; tables fbe13ac1 and 1c7acc1d).