Application of single-cell RNA sequencing on human testicular samples: a comprehensive review

Fan, Daiming; Ping, Ping; Ma, Yi; Chen, Xiang-Feng

doi:10.7150/ijbs.82191

Cited by 6 publications

(7 citation statements)

References 245 publications

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“…Furthermore, we identified novel markers for SPG (e.g., pou5f3, cd9, arhgef19, lsm14b , and klhdc1 for Undiff SPG and dnd1, smad9, mf19b and id1 for Diff SPG), some of which were also commonly highly expressed in spermatogonia of human and mice (Persio and Neuhaus, 2023; Dong et al, 2023; Itman and Loveland, 2013; Kanatsu-Shinohara et al, 2004; Niimi et al, 2019; Yokota, 2001). We also found that Undiff SPG expressed more genes involved in the maintenance of stemness and began to express genes related to differentiation in Diff SPG.…”

Section: Discussionmentioning

confidence: 99%

“…The advent of single-cell RNA sequencing (scRNA-seq) has opened new avenues for unraveling the complex gene regulatory networks underlying spermatogenesis. Recent studies in mammals have created comprehensive testicular transcriptional cell atlases and identified molecular markers for different testicular cell types (Dong et al, 2023; Guo et al, 2018; Hermann et al, 2018; Wei, et al, 2021). Although similar studies in several teleosts, such as zebrafish ( Danio rerio ) (Qian et al, 2022), black rockfish ( Sebastes schlegelii ) (Wang et al, 2023) and Chinese tongue sole ( Cynoglossus semilaevis ) (Wang et al, 2022), have begun to sketch the testicular cell landscape, our understanding of fish SSCs and testicular development during the annual reproductive cycle remains incomplete.…”

Section: Introductionmentioning

confidence: 99%

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Single-cell transcriptome unravels spermatogonial stem cells and dynamic heterogeneity of spermatogenesis in seasonal breeding teleost

Yang,

Zhou,

Wessel

et al. 2024

Preprint

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Seasonal spermatogenesis in fish is driven by spermatogonial stem cells (SSCs), which undergo a complex cellular process to differentiate into mature sperm. In this study, we characterized spermatogenesis in the large yellow croaker (Larimichthys crocea), a marine fish of significant commercial value, based on a high-resolution single-cell RNA-seq atlas of testicular cells from three distinct developmental stages- juvenile, adult differentiating and regressed testes. We detailed continuous developmental trajectory of spermatogenic cells, from spermatogonia to spermatids, elucidating the molecular events involved in spermatogenesis. We uncovered dynamic heterogeneity in cellular compositions throughout the annual reproductive cycle, accompanied by strong molecular signatures within specific testicular cells. Notably, we identified a distinct population of SSCs and observed a critical metabolic transition from glycolysis to oxidative phosphorylation, enhancing our understanding of the biochemical and molecular characteristics of SSCs. Additionally, we elucidated the interactions between somatic cells and spermatogonia, illuminating the mechanisms that regulate SSCs development. Overall, this work enhances our understanding of spermatogenesis in seasonal breeding teleost and provides essential insights for the further conservation and culture of SSCs.Summary statementOur study reveals new insights into the development of spermatogonial stem cells (SSCs), potentially impacting further conservation and culture of SSCs in teleost.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Single-cell transcriptome unravels spermatogonial stem cells and dynamic heterogeneity of spermatogenesis in seasonal breeding teleost

Yang,

Zhou,

Wessel

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…Recently, novel molecular and computational methods were also adopted, such as the metabolic and multi‐Omics employed in spermatogonial stem cell maturation and niche studies (Voigt et al., 2022; Voigt et al., 2023) and comprehensive machine learning for the identification of key genes and molecular pathways for azoospermia (He et al., 2023). Testicular scRNA‐seq data could be further extensively analysed (Dong et al., 2023), which could provide novel insights and resources for mammalian spermatogenesis research.…”

Section: Discussionmentioning

confidence: 99%

“…Single‐cell transcriptome sequencing (scRNA‐seq) is proven to be efficient and effective in disentangling the complex molecular, mechanistic, and evolutionary network of mammalian spermatogenesis in the testis (Dong et al., 2023; Hermann et al., 2018; Murat et al., 2023; Staub & Johnson, 2018; Suzuki, 2023). In humans, the first testicular scRNA‐seq study defined the cell types of spermatogonia (3), spermatocyte (7), and spermatid (4), and discovered altered gene expression patterns of testicular somatic cells for one nonobstructive azoospermia (NOA) patient (Wang et al., 2018).…”

Section: Introductionmentioning

confidence: 99%

Integrated single cell transcriptome sequencing analysis reveals species‐specific genes and molecular pathways for pig spermiogenesis

Zhao,

Yang,

2023

Reprod Domestic Animals

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Mammalian spermatogenesis is a highly complicated and intricately organized process involving spermatogonia propagation (mitosis) and meiotic differentiation into mature sperm cells (spermiogenesis). In pigs, spermatogonia development and the role of somatic cells in spermatogenesis were previously investigated in detail. However, the characterization of key molecules fundamental to pig spermiogenesis remains less explored. Here we compared spermatogenesis between humans and pigs, focusing on spermiogenesis, by integrative testicular single‐cell RNA sequencing (scRNA‐seq) analysis. Human and pig testicular cells were clustered into 26 different groups, with cell‐type‐specific markers and signalling pathways. For spermiogenesis, pseudo‐time analysis classified the lineage differentiation routes for round, elongated spermatids and spermatozoa. Moreover, markers and molecular pathways specific to each type of spermatids were examined for humans and pigs, respectively. Furthermore, high‐dimensional weighted gene co‐expression network analysis (hdWGCNA) identified gene modules specific for each type of human and pig spermatids. Hub genes (pig: SNRPD2.1 related to alternative splicing; human: CATSPERZ, Ca[2+] ion channel) potentially involved in spermiogenesis were also revealed. Taken together, our integrative analysis found that human and pig spermiogeneses involve specific genes and molecular pathways and provided resources and insights for further functional investigation on spermatid maturation and male reproductive ability.

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“…Despite being critically relevant, comprehensive reviews of recent literature revealing the dynamic landscape of single-cell testicular transcriptomics are currently limited ( 25 , 32 ). The current study dissects the spermatogenic landscapes viz., SSC/SPC niche, and cellular transcriptional dynamics during the meiotic onset and progression.…”

Section: Introductionmentioning

confidence: 99%

Understanding testicular single cell transcriptional atlas: from developmental complications to male infertility

Tirumalasetty,

Bhattacharya,

Mohiuddin

et al. 2024

Front. Endocrinol.

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Spermatogenesis is a multi-step biological process where mitotically active diploid (2n) spermatogonia differentiate into haploid (n) spermatozoa via regulated meiotic programming. The alarming rise in male infertility has become a global concern during the past decade thereby demanding an extensive profiling of testicular gene expression. Advancements in Next-Generation Sequencing (NGS) technologies have revolutionized our empathy towards complex biological events including spermatogenesis. However, despite multiple attempts made in the past to reveal the testicular transcriptional signature(s) either with bulk tissues or at the single-cell, level, comprehensive reviews on testicular transcriptomics and associated disorders are limited. Notably, technologies explicating the genome-wide gene expression patterns during various stages of spermatogenic progression provide the dynamic molecular landscape of testicular transcription. Our review discusses the advantages of single-cell RNA-sequencing (Sc-RNA-seq) over bulk RNA-seq concerning testicular tissues. Additionally, we highlight the cellular heterogeneity, spatial transcriptomics, dynamic gene expression and cell-to-cell interactions with distinct cell populations within the testes including germ cells (Gc), Sertoli cells (Sc), Peritubular cells (PTc), Leydig cells (Lc), etc. Furthermore, we provide a summary of key finding of single-cell transcriptomic studies that have shed light on developmental mechanisms implicated in testicular disorders and male infertility. These insights emphasize the pivotal roles of Sc-RNA-seq in advancing our knowledge regarding testicular transcriptional landscape and may serve as a potential resource to formulate future clinical interventions for male reproductive health.

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Application of single-cell RNA sequencing on human testicular samples: a comprehensive review

Cited by 6 publications

References 245 publications

Single-cell transcriptome unravels spermatogonial stem cells and dynamic heterogeneity of spermatogenesis in seasonal breeding teleost

Single-cell transcriptome unravels spermatogonial stem cells and dynamic heterogeneity of spermatogenesis in seasonal breeding teleost

Integrated single cell transcriptome sequencing analysis reveals species‐specific genes and molecular pathways for pig spermiogenesis

Understanding testicular single cell transcriptional atlas: from developmental complications to male infertility

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