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Biology subjects

Katona, B.

Publications and source records attributed to Katona, B..

5 recordsLinked to original sources

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↗

Expression landscape of the genetic hearing loss protein whirlin across human tissues and cell types.

Whirlin (WHRN/DFNB31) is a cytosekeltal scaffolding protein essential for the development and function of sensory cells in the inner ear and retina, yet its distribution and potential roles in other human tissues remain poorly defined. Here, we present a comprehensive expression map of whirlin by integrating bulk RNA, single-cell RNA, and antibody-based proteomics data generated as part of the Human Protein Atlas consortium. WHRN was detected in most human tissues, with highest levels observed in endocrine organs, reproductive tissues, and the nervous system. Single-cell analysis revealed that this distribution is driven by enrichment in specific cell types, including endocrine, ciliated, and specialized epithelial cells, as well as different immune cells. Immunohistochemistry confirmed broad protein expression with cell type-specific patterns consistent with transcriptomic data. Analysis of cancer tissues showed that whirlin is widely expressed, with levels generally reflecting those of corresponding normal tissues. In addition, several commonly used human cell lines were found to express endogenous WHRN. Together, this work provides the first comprehensive body-wide expression landscape of whirlin and establishes an important resource for further studies on its roles beyond hearing and vision. SUBJECTSCells; Genetics; Immunology; Peptides and proteins; Protein expression O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/713511v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@169a7corg.highwire.dtl.DTLVardef@1f87a54org.highwire.dtl.DTLVardef@27419borg.highwire.dtl.DTLVardef@1445140_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

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↗

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↗

The human secretome - the proteins secreted from human cells

The proteins secreted by human tissues (the secretome) are important for the basic understanding of human biology, but also for identification of potential targets for future diagnosis and therapy. Here, we present an annotation of all predicted secreted proteins (n=2,623) with information about their spatial distribution in the human body. A high-throughput mammalian cell factory was established to create a resource of recombinant full-length proteins. This resource was used for phenotypic assays involving {beta}-cell dedifferentiation and for development of targeted proteomics assays. A comparison between host cells, including omics analysis, shows that many of the proteins that failed to be generated in CHO cells could be rescued in human HEK293 cells. In conclusion, the human secretome has been mapped and characterized to facilitate further exploration of the human secretome.

molecular biology↗