Biology subjects

Kuscu, N.

Publications and source records attributed to Kuscu, N..

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↗

bioRxiv2026

Spatial atlas of the ovary identifies molecular events in primordial follicle activation in humans

The human ovarian reserve is established prenatally, when granulosa cells encapsulate germ cells to form a pool of quiescent primordial follicles, that ultimately determines the female reproductive and endocrine lifespan. From birth to menopause, subsets of these quiescent follicles, located in the thin outer ovarian cortex, are activated and undergo a growth programme with progressive inward migration to the inner cortex, before either undergoing atresia or, during reproductive age, ovulation. Disruption of this process may lead to infertility, metabolic disorders and early menopause, yet early follicle development remains largely poorly understood. Here, we generate the most comprehensive single-cell and spatial multiomics atlas of the human pre- and postnatal ovarian cortex, integrating transcriptomic and chromatin profiles from over four million cells obtained from fetal and newly profiled pediatric and adult donors. We resolve the early granulosa cell trajectory at unprecedented resolution and identify a retinoic acid-associated regulatory switch accompanying follicle activation. We further show that stromal fibroblasts are not homogeneous, but instead form a dynamic scaffold establishing previously unrecognised morphogen and paracrine gradients that organise the cortex into functional niches supporting quiescent, growing, and atretic follicles. Finally, we identify ovarian lipid associated macrophages (oLAMs) that localise around follicles and are likely to support tissue remodelling during folliculogenesis. Together, this atlas provides a foundational blueprint for human ovarian development and homeostasis, and provides a framework for improving strategies in fertility preservation and in vitro follicle maturation.

cell biology↗

bioRxiv2019

Glyoxal Does Not Preserve Cellular Proteins as Accurately as PFA: A Microscopical Survey of Epitopes

Chemical fixation is one of the most critical steps to retaining cellular targets as naturally as possible. Recent developments in microscopy allow sophisticated detection and measuring techniques with which spatio-temporal molecular alterations is conceivable. Here, we document the fixation competence of glyoxal (Gly), a less-toxic dialdehyde molecule, and paraformaldehyde (PFA) side-by-side (with or without Triton-X 100 permealization) in live- and fixed-cell preparations including human stem cells, spermatozoa, mouse oocytes/embryos using super-resolution microscopy. Although Gly seemed to act faster than PFA, catastrophic consequences were found not acceptable, especially in oocytes and embryos. Due to cell lysate and immunocytochemistry surveys, it was obvious that PFA is superior to Gly in retaining cellular proteins in situ with little/no background staining. In many samples, PFA revealed more reliable and consistent results regarding the protein quantity and cellular localization corresponding to previously defined patterns in the literature. Although the use of Gly is beneficial as indicated by previous reports, we concluded that it does not meet the requirement for proper fixation, at least for the tested cell types and proteins.

cell biology↗