A single-cell transcriptomic landscape of mouse testicular aging

Zhang, Wei; Xia, Siyu; Xiao, Wei; Song, Yali; Li, Tang; Cao, Min; Yang, Jing; Wang, Shuang; Li, Zhijie; Xu, Chengchao; Liu, Jianqiao; Zhao, Shan‐Chao; Yang, Chonglin; Wang, Jigang

doi:10.1016/j.jare.2022.12.007

Cited by 26 publications

(24 citation statements)

References 61 publications

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“…We initially observed undifferentiated spermatogonia (USgs) in a ring structure when projected in a 2-dimensional representation. Interestingly, we also found a similar torus structure of USgs in other publications of humans 36 as well as other mammals 33,35 . We examined the cyclical nature of USgs with two approaches, the first using the HISTA browser and the second using the dataset of HISTA as a computational validation of our findings using alternate methods.…”

Section: Resultssupporting

confidence: 88%

“…However, across various single-cell studies of the testis, there are inconsistencies in identifying and labeling these cells. For example, some studies focus on a high-scope population label such as spermatogonia 33,34 , whereas others have more refined sub-populations and unique naming structures 5,35,36 . To add to the complexity, histologically, SSC can be split in humans into Apale (Ap) and Adark (Ad) spermatogonia 37 , which are not distinct populations transcriptionally.…”

Section: Introductionmentioning

confidence: 99%

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The Human Infertility Single-cell Testis Atlas (HISTA): An interactive molecular scRNA-Seq reference of the human testis

Mahyari,

Vigh-Conrad,

Daube

et al. 2023

Preprint

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Background: The Human Infertility Single-cell Testis Atlas (HISTA) is an interactive web tool and a reference for navigating the transcriptome of the human testis. It was developed using joint analyses of scRNA-Seq datasets derived from a dozen donors, including healthy adult controls, juveniles, and several infertility cases. HISTA is very different than other websites of testis scRNA-seq data, providing visualization and hypothesis testing tools on a batch-removed and integrated dataset of 23429 genes measured across 26093 cells. Objective: The main goal of this manuscript is to describe HISTA in detail and highlight its unique and novel features. Methods: Therefore, we used HISTA as a guide for its application and demonstrated HISTA's translational capacity to follow up on two observations of biological relevance. Results: Our first analytical vignette identifies novel groupings of tightly regulated long non-coding RNA (lncRNA) molecules throughout spermatogenesis, suggesting specific functional genomics of these groupings. This analysis also found highly controlled expression of pairs of sense and antisense transcripts, suggesting conjoined regulatory mechanisms. In the next investigative vignette, we examined gene patterns in undifferentiated spermatogonia (USgs). We found the NANOS family of genes function as key drivers of transcriptomic signatures involved in human spermatogonial self-renewal programming; for the first time, demonstrating the relationship of NANOS1/2/3 transcripts in humans with scRNA-seq. Discussion and Conclusions: Using HISTA, we found new observations that contribute to unraveling the mechanisms behind transcriptional regulation and maintenance germ cells across spermatogenesis. Furthermore, our findings provide guidance on future validation studies and experimental direction. Overall, HISTA continues to be utilized in testis-related research, and thus is updated regularly with new analytical methods, visualizations, and data. We aim to have it serve as a research environment for a broad range of investigators looking to explore the testis tissue and male infertility. Availability and Implementation: HISTA is available as an interactive web tool: https://conradlab.shinyapps.io/HISTA Source code and documentation for HISTA are provided on GitHub: https://github.com/eisascience/HISTA

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Section: Resultssupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

The Human Infertility Single-cell Testis Atlas (HISTA): An interactive molecular scRNA-Seq reference of the human testis

Mahyari,

Vigh-Conrad,

Daube

et al. 2023

Preprint

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“…The number of obtained spermatozoa decreased; however, they did not belong to the structural epididymal cells. Confounding factors during sample processing might affect the number of identified cells; thus, we calculated the proportions/frequencies of cell types in the total epididymal cells [ 20 , 21 ]. The frequencies of principal cells, T cells, and monocytes increased, whereas those of basal, endothelial, and myoid cells decreased with age (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Studies on humans and rodents have shown that age has a progressive effect on male fertility [ 41 ]. Much attention has been paid to the effects of aging on the testes [ 21 , 42 ]. From a clinical perspective, asthenospermia is the most common manifestation of abnormal semen parameters compared with sperm concentration/count, normal morphology rate, or semen volume in elderly men [ 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing reveals the local cell landscape in mouse epididymal initial segment during aging

Liu

Yao

et al. 2023

Immun Ageing

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Background Morphological and functional alterations in aging reproductive organs result in decreased male fertility. The epididymis functions as the transition region for post-testicular sperm maturation. And we have previously demonstrated that the epididymal initial segment (IS), a region of the reproductive tract essential for sperm maturation and capacitation, undergoes considerable histological changes and chronic immune activation in mice during aging. However, the local aging-associated cellular and molecular changes in the aged epididymal IS are poorly understood. Results We conducted single-cell RNA sequencing analysis on the epididymal IS of young (3-month-old) and old (21-month-old) mice. In total, 10,027 cells from the epididymal IS tissues of young and old mice were obtained and annotated. The cell composition, including the expansion of a principal cell subtype and Ms4a4bHiMs4a6bHi T cells, changed with age. Aged principal cells displayed multiple functional gene expression changes associated with acrosome reaction and sperm maturation, suggesting an asynchronous process of sperm activation and maturation during epididymal transit. Meanwhile, aging-related altered pathways in immune cells, especially the “cell chemotaxis” in Cx3cr1Hi epididymal dendritic cells (eDCs), were identified. The monocyte-specific expression of chemokine Ccl8 increased with age in eDCs. And the aged epididymal IS showed increased inflammatory cell infiltration and cytokine secretion. Furthermore, cell–cell communication analysis indicated that age increased inflammatory signaling in the epididymal IS. Conclusion Contrary to the general pattern of lower immune responses in the male proximal genital tract, we revealed an inflammaging status in mouse epididymal initial segment. These findings will allow future studies to enable the delay of male reproductive aging via immune regulation.

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“…Compared with the bulk RNA-seq method that determines RNA information of mixed cell population, single-cell RNA sequencing (scRNA-seq) enables comprehensive detection of the transcriptional information of individual cells, expanding our understanding of cellular heterogeneity. [14][15][16][17] Therefore, scRNA-seq advanced our knowledge of biological processes and toxicology studies at a high resolution. For instance, scRNA-seq has been used to dissect liver injury and diseases in both human and animal models, [18][19][20][21] providing comprehensive insights into the underlying mechanisms in different cell types of liver tissues.…”

Section: Introductionmentioning

confidence: 99%

Insight into Tetrabromobisphenol A‐Associated Liver Transcriptional Landscape via Single Cell RNA Sequencing

Bai,

Zhu,

et al. 2023

Advanced Biology

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In recent years, there has been growing concern over the rising incidence of liver diseases, with increasing exposure to environmental toxins as a significant contributing factor. However, the mechanisms of liver injury induced by environmental pollutants are largely unclear. Here, using tetrabromobisphenol A (TBBPA), a widely used brominated flame retardant, as an example, environmental toxin‐induced liver toxicity in mice is characterized via single‐cell sequencing technology. Heterogeneous gene expression profiles after exposure to TBBPA in major cell types of the liver are demonstrated. In hepatocytes, pathway analysis of differentially expressed genes reveals the enhanced interferon response and diminished metabolic processes. The disrupted endothelial functions in TBBPA‐treated cells are then shown. Moreover, the activation of M2‐polarization in Kupffer cells, as well as activated effector T and B cells are unveiled in TBBPA‐treated cells. Finally, ligand‐receptor pair analysis shows that TBBPA disrupts cell‐cell communication and induces an inflammatory microenvironment. Overall, the results reveal that TBBPA‐induced dysfunction of hepatocytes and endothelial cells may then activate and recruit other immune cells such as Kuffer cells, and T/NK cells into the liver, further increasing inflammatory response and liver injury. Thus, the results provide novel insight into undesiring environmental pollutant‐induced liver injury.

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A single-cell transcriptomic landscape of mouse testicular aging

Cited by 26 publications

References 61 publications

The Human Infertility Single-cell Testis Atlas (HISTA): An interactive molecular scRNA-Seq reference of the human testis

The Human Infertility Single-cell Testis Atlas (HISTA): An interactive molecular scRNA-Seq reference of the human testis

Single-cell RNA sequencing reveals the local cell landscape in mouse epididymal initial segment during aging

Insight into Tetrabromobisphenol A‐Associated Liver Transcriptional Landscape via Single Cell RNA Sequencing

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