Biology subjects

Schissel, T.

Publications and source records attributed to Schissel, T..

3 recordsLinked to original sources

bioRxiv2026

An integrated multimodal pan-organ atlas of the female reproductive system across the lifespan contextualises gynaecological pathologies

Single cell transcriptomics has transformed our knowledge of reproductive tissues, yet studies remain largely organ-specific and temporally limited, leaving an incomplete picture of how cell types are distributed across the reproductive system over a lifetime. Gynaecological conditions affect more than one in four females and frequently span multiple organs and life stages. To advance our understanding and treatment of these conditions, an integrated cellular reference is essential. Here we present the Human Female Reproductive System Cell Atlas v1: a single-cell transcriptomic resource integrating more than 2M cells across the ovary, fallopian tube, uterus, cervix and vagina over the lifespan and menstrual cycle, further integrated with spatial transcriptomics and chromatin accessibility profiling to define 210 cell types through community-based annotation. Cross-organ integration resolves shared and organ-specific cellular states, identifying uterine-specific perivascular populations lining uterine spiral arteries, hypoxia-sensing type 3 innate lymphoid cells (ILC3s) enriched in the uterus, and lipid-associated macrophages with distinct subsets in each reproductive organ, including a previously undescribed population shared between the uterus and fallopian tube. Cross-organ integration enables detection of ectopic epithelial populations in otherwise healthy donors, including endometrial-like cells within a paediatric ovary consistent with early endometriosis. Integration with genome-wide association studies (GWAS) reveals that risk variants for major gynecological conditions act in mesenchymal cell states defined by specific transcriptional programmes and spatial or temporal context - for instance, heavy menstrual bleeding risk is enriched in basal fibroblasts (SFRP5) of the regenerative endometrial compartment. An integrated chromatin accessibility atlas provides peak-to-gene maps across reproductive cell types, enabling nomination of disease effector genes and providing the first regulatory evidence linking a Polyendocrine Metabolic Ovarian Syndrome (PMOS) risk locus to INHBB in granulosa cells. Together, this resource establishes a cellular and molecular framework for reproductive biology and the pathogenesis of neglected gynaecological conditions.

Cell Biology↗

bioRxiv2025

Transcriptomic and proteomic dynamics of ovarian follicle group culture resemble in vivo folliculogenesis

The prohibitively low yield of fertilizable oocytes obtained from cultured ovarian follicles limits clinical translation of in vitro follicle maturation for fertility preservation. This is in part due to an incomplete understanding of the process of follicle development. Previous work has demonstrated that group culture of primary murine follicles had a synergistic effect on growth and maturation in contrast to single follicles, but mechanisms remained unknown. Here, we cultured primary follicles in groups of 5 (5X) or 10 (10x) for twelve days, separated the somatic cells from oocytes, and analyzed the temporal transcriptional signatures every two days. In total, 13,461 genes in somatic cells and 10,091 genes in oocytes were computationally sorted into ten temporally distinct gene expression patterns. The somatic cell temporal gene expression patterns showed strong concordance with the granulosa and theca cell markers reported in a recent single-cell whole ovary RNA sequencing study. Importantly, canonical markers of steroidogenesis in cultured follicles followed expected trajectories of decreasing Amh expression and increasing Inhba, Inhbb, Cyp11a1, Cyp17a1, Cyp19a1, Lhcgr, and Fshr over the culture period. Furthermore, when comparing the 10X and 5X culture groups, we identified 306 and 14 differentially expressed genes in somatic cells and oocytes, respectively. Shotgun proteomics data was aligned with the somatic cell transcriptomic data and identified four L-R pairs that were differentially expressed between the two conditions. These comprehensive datasets uncovered temporal dynamics of in vitro folliculogenesis in a compartment-specific manner, serving as a valuable resource for optimizing future follicle culture systems for fertility preservation.

cell biology↗

bioRxiv2025

Single-oocyte transcriptional profile of early-stage human oocytes reveals differentially expressed genes in the primordial and transitioning stages.

The critical initial step in human oocyte maturation - the transition of ovarian follicles from dormancy to activation - remains poorly understood. Here we performed RNA sequencing on single oocytes isolated from early-stage follicles from nine healthy reproductive-age donors. Data for 133 high-quality oocytes formed two connected clusters, C1 and C2, with 5,449 significantly differentially expressed genes. Using recently reported gene lists for early-stage follicles we found that C1 oocytes likely came from earlier, dormant primordial follicles, while C2 oocytes match later-stage primordial or transitioning follicles. We sought to validate two DE genes, UHRF1 for C1 and CCN2 for C2, by their RNA-FISH in situ pattern in morphologically classified follicles, but did not observe statistically significant differences between follicle stages. This apparent discrepancy between follicles stage determined by its morphology and oocytes transcriptional state, if replicated in additional studies, may indicate a lack of closely coupled synchrony between follicle morphology and oocytes functional state.

cell biology↗