Biology subjects

Hikmet, F.

Publications and source records attributed to Hikmet, F..

7 recordsLinked to original sources

bioRxiv2026

Pubertal maturation and chemotherapy-associated disruption of the pediatric ovary revealed by multimodal single-cell profiling

Ovarian tissue cryopreservation enables fertility preservation in females undergoing gonadotoxic therapies, restoring fertility in adults. Although offered even before puberty, the childhood ovary and its vulnerability to therapy remain poorly characterized. Here, ovarian tissue from 16 patients undergoing fertility preservation (aged 1-16 years) and 11 adult controls (aged 22-32 years) was analyzed using single-cell RNA sequencing, spatial transcriptomics, and multiplex immunostaining. In chemotherapy-naive samples, 13 somatic cell populations underwent extracellular matrix remodeling, vascular, neural, and stromal maturation during puberty, whereas changes in germline related to chromatin remodeling. Spatial transcriptomics resolved 23 clusters across, revealing distinct tissue organization and follicular niche composition between children and adults. Chemotherapy exposure depleted perifollicular and vascular cells, suppressed intercellular signaling, and dysregulated over half of puberty-associated genes, converging on stress responses and extracellular matrix remodeling, with SEPTIN7 as a potential biomarker. These findings uncover critical developmental vulnerabilities of the pediatric ovary relevant to fertility preservation.

developmental biology↗

bioRxiv2026

Regional epithelial architecture and spatial distribution of T and B lymphocytes in the human fallopian tube

The human fallopian tube plays a critical role in reproduction, yet its structural organization and immune landscape remain incompletely characterized. Here, we analyzed tissue from women of reproductive age across three anatomical regions (isthmus, ampulla, and fimbriae) throughout the menstrual cycle. By using antibody-based imaging together with automated image analysis, the epithelial thickness and spatial distribution of T and B lymphocytes was assessed. No significant differences in epithelial thickness were observed between proliferative and secretory phases. However, significant regional variation was identified, with the epithelium thickest in the isthmus and thinnest in the ampulla. Both CD8A+ T lymphocytes and CD20+ B lymphocytes were present throughout the fallopian tube, with their abundance strongly correlated across patients. Spatial analysis further revealed that both lymphocyte populations were preferentially localized to the mucosal compartment adjacent to the lumen, and intraepithelial B lymphocytes were consistently observed. Together, these findings provide new insight into epithelial organization and immune cell distribution in the human fallopian tube, highlighting the complexity of the tubal immune microenvironment and its potential relevance for reproductive biology.

immunology↗

bioRxiv2026

A high-resolution spatial map of cilia-associated proteins in the human fallopian tube

Molecular alterations in the fallopian tubes play a pivotal role in the development of cancer and reproductive disorders, yet their molecular landscape at the protein level remains poorly defined. Here, we map key fallopian tube proteins at single-cell resolution utilizing an integrated transcriptomics and proteomics approach. Based on RNA-seq analysis we identify 310 genes with elevated expression in fallopian tube, the majority of which are associated with motile cilia function. We spatially characterize 133 of the corresponding proteins in fallopian tube and other human tissues with motile cilia to subcellular structures of ciliated cells, validating the findings with single-cell RNA-seq and mass-spectrometry data. Eleven proteins previously only studied on the transcript level without information in cilia databases are further analyzed in a hydrosalpinx patient, showing a thinner epithelium, lower density of FOXJ1 expression, and reduced expression of FHAD1, RIIAD1, and C2orf81. Our high-resolution spatial map aids in dissecting the pathways underlaying infertility and diseases linked to cilia-specific functions.

molecular biology↗

bioRxiv2025

A high-resolution subcellular map of proteins in ciliated cells

Motile cilia are complex structures regulated by thousands of genes, essential for various physiological functions like respiration and reproduction. Their dysfunction can result in severe conditions like primary ciliary dyskinesia (PCD), highlighting the need for a deeper molecular understanding of their specific ciliary compartments. Interestingly, ciliated cells harbor multiple proteins with limited evidence on biological function, as defined by Functional Evidence (FE) scores, a grading system developed by the Human Proteome Project (HPP). Building upon the stringent antibody validation pipeline of the Human Protein Atlas (HPA) project, we developed a high-throughput workflow that combines a novel multiplex immunohistochemistry protocol with image analysis to investigate protein expression and subcellular localization in motile ciliated cells across five human tissues: nasopharynx, bronchus, fallopian tube, endometrium, and cervix. We spatially mapped >180 proteins, out of which 73% have FE scores 2-5, suggesting that further evidence is needed to establish these proteins biological function. Notably, expression patterns varied between tissues, suggesting that motile cilia proteins are not universally expressed across the different epithelia. Our pipeline constitutes a promising resource for comprehensive mapping of the motile cilia proteome, and a first step towards identifying cilia proteins for functional studies to understand the molecular mechanisms underlying ciliopathies.

cell biology↗

bioRxiv2024

A spatiotemporal atlas of human spermatogenesis based on single-cell transcriptomics and multiplex antibody imaging

Understanding how transcriptional programs are translated into functional protein landscapes within intact tissues remains a major challenge in biology. While single-cell RNA sequencing (scRNA-seq) has enabled high-resolution identification of cellular states, corresponding protein expression within its spatial context remains poorly resolved at scale. Here, we present a scalable framework that integrates scRNA-seq with multiplex immunohistochemistry (mIHC) and automated image analysis to achieve spatially resolved, single-cell-level protein mapping across human spermatogenesis. Using this approach, we quantified the expression of nearly 500 proteins across 12 discrete germ cell states within intact human testis tissue, generating a high-resolution spatiotemporal proteomic atlas. Comparative analysis of mRNA and protein expression revealed widespread temporal discordance, indicating that transcriptional state is not always predictive of protein abundance. Notably, we identify delayed translation of key regulators such as PIWIL4, whose protein expression peaks at later differentiation stages than its mRNA expression. Together, our results establish a generalizable strategy for proteome-wide spatial mapping of single-cell states and demonstrate the importance of integrating protein-level measurements to resolve cellular identity and function in complex tissues.

molecular biology↗

bioRxiv2022

Genome-wide single cell annotation of the human protein-coding genes

An important quest for the life science community is to deliver a complete annotation of the human building-blocks of life, the genes and the proteins. Here, we report on a genome-wide effort to annotate all protein-coding genes based on single cell transcriptomics data representing all major tissues and organs in the human body, integrated with data from bulk transcriptomics and antibody-based tissue profiling. Altogether, 25 tissues have been analyzed with single cell transcriptomics resulting in genome-wide expression in 444 single cell types using a strategy involving pooling data from individual cells to obtain genome-wide expression profiles of individual cell type. We introduce a new genome-wide classification tool based on clustering of similar expression profiles across single cell types, which can be visualized using dimensional reduction maps (UMAP). The clustering classification is integrated with a new "tau" score classification for all protein-coding genes, resulting in a measure of single cell specificity across all cell types for all individual genes. The analysis has allowed us to annotate all human protein-coding genes with regards to function and spatial distribution across individual cell types across all major tissues and organs in the human body. A new version of the open access Human Protein Atlas (www.proteinatlas.org) has been launched to enable researchers to explore the new genome-wide annotation on an individual gene level.

systems biology↗

bioRxiv2020

The protein expression profile of ACE2 in human tissues

The novel SARS-coronavirus 2 (SARS-CoV-2) poses a global challenge on healthcare and society. For understanding the susceptibility for SARS-CoV-2 infection, the cell type-specific expression of the host cell surface receptor is necessary. The key protein suggested to be involved in host cell entry is Angiotensin I converting enzyme 2 (ACE2). Here, we report the expression pattern of ACE2 across >150 different cell types corresponding to all major human tissues and organs based on stringent immunohistochemical analysis. The results were compared with several datasets both on the mRNA and protein level. ACE2 expression was mainly observed in enterocytes, renal tubules, gallbladder, cardiomyocytes, male reproductive cells, placental trophoblasts, ductal cells, eye and vasculature. In the respiratory system, the expression was limited, with no or only low expression in a subset of cells in a few individuals, observed by one antibody only. Our data constitutes an important resource for further studies on SARS-CoV-2 host cell entry, in order to understand the biology of the disease and to aid in the development of effective treatments to the viral infection.

cell biology↗