Single-cell analysis of human testis aging and correlation with elevated body mass index

Nie, Xiaolu; Munyoki, Sarah; Sukhwani, Meena; Schmid, Nina; Missel, Annika; Emery, Benjamin R.; DonorConnect,; Stukenborg, Jan-Bernd; Mayerhofer, Artur; Orwig, Kyle E.; Aston, Kenneth I.; Hotaling, James M.; Cairns, Bradley R.; Guo, Jingtao

doi:10.1016/j.devcel.2022.04.004

Cited by 85 publications

(91 citation statements)

References 70 publications

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“…Please note that for the comparison, we used the data from a man (N3; 55 years old) which closely matched the donors of our cells with respect to age and obstructive azoospermia. Of note, similar to our study, Nie et al [ 17 ] and Di Persio et al [ 3 ] used the same platform (10x Genomics).…”

Section: Methodssupporting

confidence: 67%

“…In addition, we mined the publicly available human testis scRNAseq data (Nie et al [ 17 ]; NIH Gene expression Omnibus (GEO): GSE182786), which contain information about young adult men (17–22 years old). We also examined the publicly available data (Di Persio et al [ 3 ]; NIH Gene expression Omnibus (GEO): GSE153947), which contain information on testicular cells from men with obstructive azoospermia.…”

Section: Methodsmentioning

confidence: 99%

“…As these cells form a small compartment within the testis, the mentioned previous ex vivo analyses are based on a few hundred peritubular cells (e.g., 900 cells in Nie et al [ 17 ] from four patients; 550 cells in Di Persio et al [ 3 ] from one patient), a limitation that, as we have reasoned, can be overcome by studying cultured cells, provided that they reflect the in situ situation and retain their phenotype.…”

Section: Introductionmentioning

confidence: 99%

“…We studied cultured HTPCs and performed single-cell RNA seq analyses. We compared the results with own data, including proteomic results, the in situ protein data available in the Human Protein Atlas ( ; accessed on 1 April 2022), and transcriptomic information available (Nie et al [ 17 ], selection of young patients; Di Persio et al [ 3 ]). Based on results, which indicated the expression of mesenchymal stromal cell (MSC) characteristics and hints of retinoic acid synthesis, we performed additional studies to explore the plasticity and differentiation potential of HTPCs and we examined their ability to produce retinoic acid.…”

Section: Introductionmentioning

confidence: 99%

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The Molecular Signature of Human Testicular Peritubular Cells Revealed by Single-Cell Analysis

Liebich

Schmid

Koupourtidou

et al. 2022

Cells

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Peritubular cells of the human testis form a small compartment surrounding the seminiferous tubules. They are crucial for sperm transport, and they emerge as contributors to the spermatogonial stem cell niche. They are among the least known cell types of the human body. We employed single-cell RNA sequencing of cultured human testicular peritubular cells (HTPCs), which had been isolated from testicular samples of donors with normal spermatogenesis. The significant overlap between our results and recently published ex vivo data indicates that HTPCs are a highly adequate cellular model to define and study these cells. Thus, based on the expression of several markers, HTPCs can be classified as testicular smooth muscle cells. Small differences between the in vivo/in vitro expressed genes may be due to cellular plasticity. Plasticity was also shown upon addition of FCS to the culture medium. Based on transcriptome similarities, four cellular states were identified. Further analyses confirmed the presence of known stem cell niche-relevant factors (e.g., GDNF) and identified unknown functions, e.g., the ability to produce retinoic acid. Therefore, HTPCs allow us to define the signature(s) and delineate the functions of human testicular peritubular cells. The data may also serve as a resource for future studies to better understand male (in)fertility.

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Section: Methodssupporting

confidence: 67%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Molecular Signature of Human Testicular Peritubular Cells Revealed by Single-Cell Analysis

Liebich

Schmid

Koupourtidou

et al. 2022

Cells

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“…A study shows that testicular aging is closely related to body mass index (BMI) in the elderly. Older men with higher BMI have more severe testicular aging changes ( 58 ). Elucidating the mechanisms leading to reproductive senescence under these physiological or pathological conditions can facilitate the development of precisely targeted therapies for pathological testicular premature aging by detecting or intervening at key nodes in the future.…”

Section: Aging and Spermatogenesismentioning

confidence: 99%

Testicular aging, male fertility and beyond

Dong

Chen²,

Zhang³

et al. 2022

Front. Endocrinol.

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Normal spermatogenesis and sperm function are crucial for male fertility. The effects of healthy testicular aging and testicular premature aging on spermatogenesis, sperm function, and the spermatogenesis microenvironment cannot be ignored. Compared with younger men, the testis of older men tends to have disturbed spermatogenic processes, sperm abnormalities, sperm dysfunction, and impaired Sertoli and Leydig cells, which ultimately results in male infertility. Various exogenous and endogenous factors also contribute to pathological testicular premature aging, such as adverse environmental stressors and gene mutations. Mechanistically, Y-chromosomal microdeletions, increase in telomere length and oxidative stress, accumulation of DNA damage with decreased repair ability, alterations in epigenetic modifications, miRNA and lncRNA expression abnormalities, have been associated with impaired male fertility due to aging. In recent years, the key molecules and signaling pathways that regulate testicular aging and premature aging have been identified, thereby providing new strategies for diagnosis and treatment. This review provides a comprehensive overview of the underlying mechanisms of aging on spermatogenesis. Furthermore, potential rescue measures for reproductive aging have been discussed. Finally, the inadequacy of testicular aging research and future directions for research have been envisaged to aid in the diagnosis and treatment of testicular aging and premature aging.

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Mapping Cell Atlases at the Single‐Cell Level

Ye,

Wang,

et al. 2023

Advanced Science

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Recent advancements in single‐cell technologies have led to rapid developments in the construction of cell atlases. These atlases have the potential to provide detailed information about every cell type in different organisms, enabling the characterization of cellular diversity at the single‐cell level. Global efforts in developing comprehensive cell atlases have profound implications for both basic research and clinical applications. This review provides a broad overview of the cellular diversity and dynamics across various biological systems. In addition, the incorporation of machine learning techniques into cell atlas analyses opens up exciting prospects for the field of integrative biology.

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Single-cell analysis of human testis aging and correlation with elevated body mass index

Cited by 85 publications

References 70 publications

The Molecular Signature of Human Testicular Peritubular Cells Revealed by Single-Cell Analysis

The Molecular Signature of Human Testicular Peritubular Cells Revealed by Single-Cell Analysis

Testicular aging, male fertility and beyond

Mapping Cell Atlases at the Single‐Cell Level

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