Single-cell Transcriptome Atlas of Testis Aging
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE215754 | GEO | 2022/10/17
REPOSITORIES: GEO
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Project description:Aging human males display reduced reproductive health, however testis aging is poorly understood at the molecular and genomic level. Here, we utilized single-cell RNA-seq to profile over 44,000 cells from both young and older men (>60 years old) – and examined age-related changes in germline development and in the somatic niche. Interestingly, age-related changes in spermatogonial stem cells appeared modest, whereas age-related dysregulation of spermatogenesis and the somatic niche ranged from moderate to severe. Altered pathways included signaling and inflammation in multiple cell types, metabolic signaling in Sertoli cells, hedgehog signaling and testosterone production in Leydig cells, cell death and growth in testicular peritubular cells, and possible developmental regression in both Leydig and peritubular cells. Remarkably, the extent of dysregulation correlated with body mass index in older, but not younger men. Taken together, we reveal candidate molecular mechanisms underlying the complex testicular changes conferred by aging, and their exacerbation by concurrent chronic conditions such as obesity.
2022-05-05 | GSE182786 | GEO
Project description:In humans, the most common sex chromosomal disorder is Klinefelter syndrome (KS), caused by the presence of one or more extra X-chromosomes. The KS patients display a diverse adult phenotype with increased height, gynaecomastia, and hypergonadotropic hypogonadism as the most common symptoms. Men with KS are almost always infertile due to testicular degeneration, which accelerates during puberty. Very few studies investigated when the germ cell loss begins and whether it is caused by dysgenetic fetal development of the testes. We investigated a series of fetal KS testis tissue samples and found a marked reduction in MAGE-A4-positive pre-spermatogonia in the developing KS gonads compared to controls, indicating a failure of the gonocytes to differentiate into pre-spermatogonia. Transcriptome analysis by RNA sequencing of formalin-fixed and paraffin embedded gonads originating from 4 fetal KS samples and 5 age- and cellularity-matched controls revealed 211 differentially expressed transcripts in the fetal KS testis. We found a significant enrichment of upregulated X-chromosomal transcripts and validated the expression of the pseudoautosomal region 1 (PAR1) gene, AKAP17A. Moreover, we found enrichment of long non-coding RNAs in the KS testes (e.g. LINC01569 and RP11-485F13.1). In conclusion, our data indicates that the testicular phenotype observed among adult men with KS is initiated already in fetal life by failure of the gonocyte differentiation into pre-spermatogonia, which could be due to aberrant expression of long non-coding RNAs.
2018-08-28 | GSE103613 | GEO
Project description:As a unique population of testicular mesenchymal stromal cells, stem Leydig cells (SLCs) have shown great promise in the treatment of male hypogonadism. The therapeutic functions of MSCs are largely determined by their reciprocal regulation by immune responses. However, the immunoregulatory properties of SLCs have not been fully studied. Here, we found that transplanted SLCs restored testicular immunological homeostasis via damage signal-triggered transient receptor potential cation channel subfamily member 7 (TRPM7)-mediated mitochondrial transfer to macrophages. Specifically, the results showed that SLCs transplantation restored male fertility and testosterone production in an ischemia‒reperfusion injury-induced acute inflammation model. This was achieved mainly via a mechanism involving the prevention of inflammatory cascades but not the differentiation to Leydig cells (LCs), the main testosterone-producing cells. Furthermore, we identified that ROS released from activated macrophages, which are the primary testicular immunocytes, induced nanotube-mediated mitochondrial transfer from SLCs to macrophages via TRPM7. Notably, TRPM7 knockdown by interfering RNA in transplanted SLCs compromised the therapeutic outcomes in both testicular ischemia‒reperfusion and testicular aging mouse models. Collectively, SLC rescued testicular damage in testicular ischemia‒reperfusion mouse models, and the damage signal activated TRPM7 signaling and induced mitochondrial transfer from SLCs to macrophages, playing important roles in the repair of SLCs. These findings provide insight into the clinical translation of SLCs and suggest that strategies targeting mitochondrial transfer may be effective treatments for patients with male hypogonadism related to immune disorders.
2024-02-01 | GSE254881 | GEO
Project description:In humans, the most common sex chromosomal disorder is Klinefelter syndrome (KS), caused by the presence of one or more extra X-chromosomes. The KS patients display a diverse adult phenotype with increased height, gynaecomastia, and hypergonadotropic hypogonadism as the most common symptoms. Men with KS are almost always infertile due to testicular degeneration, which accelerates during puberty. Very few studies investigated the global gene expression analysis of adult KS testes and, more importantly, which cell types the differentially expressed transcripts originate from. Transcriptome analysis by RNA sequencing of fixed and paraffin embedded testes originating from 3 adult KS samples and 3 adult cellularity-matched controls revealed 236 differentially expressed transcripts in the adult KS testis. To examine the cellular origin of the differentially expressed transcripts, transcriptome profiling was also carried out on 4 testes with Sertoli Cell-Only and 4 testes with full spermatogenesis. Also, pre-pubertal KS and controls were RNA-sequenced.
2018-05-30 | GSE103905 | GEO
Project description:Testicular biopsies were extracted surgically from men presenting with different states of spermatogenic impairments. The biopsies were scored histologically according to the Johnsen score system and microarrray technology was applied in order to correlate the gene expression pattern with the morphological categorization. Keywords: disease state analysis
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Project description:Identification of gene expression patterns that correlate with distinct stages of male germ cell development using biopsies from men with highly defined and homogenous testicular pathologies based on the Johnsen score procedure. The Johnsen score procedure is a classical histopathological scoring procedure that classifies the germ cell composition from different stages of spermatogenic impairment.
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Project description:The aim of this investigation was to develop a global view of muscle transcriptional differences between older men and women and with aging for each sex. Muscle biopsies were obtained from the biceps brachii of young (age 19~28yrs) and older (age 65~76 yrs) men (7 young, 4 older) and women (7 young, 4 older). Total RNA was extracted and gene expression profiling was performed using the Affymetrix Human Genome U133 Plus 2 chip.
2013-02-28 | E-GEOD-38718 | biostudies-arrayexpress
Project description:Human testis development in prenatal life involves complex changes in germline and somatic cell identity. To better understand, we profiled and analyzed ~32,500 single-cell transcriptomes of testicular cells from embryonic, fetal and infant stages. Our data shows that at 6-7 weeks post-fertilization as the testicular cords are established, the Sertoli and interstitial cells originate from a common heterogeneous progenitor pool, which then resolves into fetal Sertoli cells (expressing tube-forming genes) or interstitial cells (including Leydig-lineage cells expressing steroidogenesis genes). Almost ten weeks later, beginning at 15-16 weeks post-fertilization, the male primordial germ cells exit mitosis, downregulate pluripotent transcription factors and transition into cells that strongly resemble the ‘State 0’ spermatogonia originally defined in the infant and adult testes. Therefore, we termed these fetal spermatogonia ‘State f0’. Taken together, we reveal multiple insights into the coordinated and temporal development of the embryonic, fetal and postnatal male germline together with the somatic niche.
2021-01-18 | GSE161617 | GEO
Project description:The successful proliferation and differentiation of testicular cells are vital for the survival, continuity and preservation of species. However, a comprehensive molecular orchestration underlying the spermatogenic process in teleost testis development throughout the annual cycle remains elusive. In this study, the testicular cells derived from adult black rockfish at distinct stages—Regressed, Regenerating, and Differentiating were dissected via single cell transcriptome sequencing. A continuous developmental trajectory of spermatogenic cells, from spermatogonia to spermatids, was delineated, elucidating the molecular events involved in the spermatogonia development. Subsequently, the dynamic regulation of gene expressions associated with spermatogonia proliferation and differentiation was observed across spermatogonia subgroups and various developmental stages. A bioenergetic transition from glycolysis to mitochondrial respiration of spermatogonia during annual developmental cycle was demonstrated, and a deeper level of heterogeneity and molecular characteristics was revealed by re-clustering analysis. The developmental trajectory of Sertoli cells in annual reproductive cycle was examined, and the divergence of Leydig cells and macrophage were explored. Additionally, the interaction network between testicular micro-environment somatic cells and spermatogenic cell were established. Overall, our study provides detailed information on both germ and somatic cells within teleost testis during annual reproductive cycle, along with insights into the molecular regulation of spermatogonia dynamics, which lay the foundation for spermatogenesis regulation and germplasm preservation of endangered species.
2024-02-26 | GSE252438 | GEO
Project description:Human adult spermatogenesis balances spermatogonial stem cell (SSC) self-renewal and differentiation, alongside complex germ cell-niche interactions, to ensure long-term fertility and faithful genome propagation. Here, we performed single-cell RNA sequencing of ~6500 testicular cells from young adults. We found five niche/somatic cell types (Leydig, myoid, Sertoli, endothelial, macrophage), and observed germline-niche interactions and key human-mouse differences. Spermatogenesis, including meiosis, was reconstructed computationally, revealing sequential coding, non-coding, and repeat-element transcriptional signatures. Interestingly, we identified five discrete transcriptional/developmental spermatogonial states, including a novel early SSC state, termed State 0. Epigenetic features and nascent transcription analyses suggested developmental plasticity within spermatogonial States. To understand the origin of State 0, we profiled testicular cells from infants, and identified distinct similarities between adult State 0 and infant SSCs. Overall, our datasets describe key transcriptional and epigenetic signatures of the normal adult human testis, and provide new insights into germ cell developmental transitions and plasticity.
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