An atlas of cell types in the mouse epididymis and vas deferens

Rinaldi, Vera D.; Donnard, Elisa; Gellatly, Kyle; Rasmussen, Morten; Küçükural, Alper; Yukselen, Onur; Garber, Manuel; Sharma, Upasna; Rando, Oliver J.

doi:10.7554/elife.55474

Cited by 67 publications

(82 citation statements)

References 110 publications

(142 reference statements)

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“…Consistent with a recent study 37 , epididymal supporting cells were also identified. These include myoid cells/fibroblasts (C1) for contraction of the myoid to promote sperm movement and form an extracellular environment 2 , 37 , 51 , macrophages/monocytes (C3) for immune equilibrium 52 , and endothelial cells (C6) for composing blood and lymph vessels 37 . In addition to epididymal cells, sperm (C7) were also identified because of the whole epididymis dissociation applied in our study.…”

Section: Discussionsupporting

confidence: 90%

“…Accumulating studies have attempted to characterize the cell types in the epididymis based on cell location, morphology, connection, function, and marker gene expression 34 – 36 . A scRNA-seq dataset from the mouse genital duct was recently reported 37 . While our results are consistent with a previous report on the clustering of general cell types, our study provided an in-depth analysis of biological replicates.…”

Section: Discussionmentioning

confidence: 99%

“…To validate the expression of mitochondrial genes in epididymal cells, sperm-depleted dissection of the epididymis was performed according to the previous description 37 . Of note, the epididymis segment (caput, corpus, and cauda) separation followed the conventional illustration 7 , 84 .…”

Section: Methodsmentioning

confidence: 99%

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Spatio-temporal landscape of mouse epididymal cells and specific mitochondria-rich segments defined by large-scale single-cell RNA-seq

et al. 2021

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Spermatozoa acquire their fertilizing ability and forward motility during epididymal transit, suggesting the importance of the epididymis. Although the cell atlas of the epididymis was reported recently, the heterogeneity of the cells and the gene expression profile in the epididymal tube are still largely unknown. Considering single-cell RNA sequencing results, we thoroughly studied the cell composition, spatio-temporal differences in differentially expressed genes (DEGs) in epididymal segments and mitochondria throughout the epididymis with sufficient cell numbers. In total, 40,623 cells were detected and further clustered into 8 identified cell populations. Focused analyses revealed the subpopulations of principal cells, basal cells, clear/narrow cells, and halo/T cells. Notably, two subtypes of principal cells, the Prc7 and Prc8 subpopulations were enriched as stereocilia-like cells according to GO analysis. Further analysis demonstrated the spatially specific pattern of the DEGs in each cell cluster. Unexpectedly, the abundance of mitochondria and mitochondrial transcription (MT) was found to be higher in the corpus and cauda epididymis than in the caput epididymis by scRNA-seq, immunostaining, and qPCR validation. In addition, the spatio-temporal profile of the DEGs from the P42 and P56 epididymis, including transiting spermatozoa, was depicted. Overall, our study presented the single-cell transcriptome atlas of the mouse epididymis and revealed the novel distribution pattern of mitochondria and key genes that may be linked to sperm functionalities in the first wave and subsequent wave of sperm, providing a roadmap to be emulated in efforts to achieve sperm maturation regulation in the epididymis.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Spatio-temporal landscape of mouse epididymal cells and specific mitochondria-rich segments defined by large-scale single-cell RNA-seq

et al. 2021

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“…Therefore, it was excluded from further analysis. Finally, we identified two clusters (P.Epi and B.Epi) as basal epididymal cells and principal epididymal cells based on marker genes (fig S2b) (Rinaldi et al, 2020). Because the epididymis is located close to the EPI depot, epididymal cells included in the EPI adipose are likely a dissection artifact, and they were not included in the analysis.…”

Section: Resultsmentioning

confidence: 99%

Single-cell Chromatin Accessibility and Lipid Profiling Reveals a Metabolic Shift in Adipocytes Induced by Bariatric Surgery

Harlan

Hg²,

Spektor

et al. 2021

Preprint

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Obesity promotes type 2 diabetes and cardiometabolic pathologies. Vertical sleeve gastrectomy (VSG) is used to treat obesity resulting in long-term weight loss and health improvements that precede weight loss; however, the mechanisms underlying the immediate benefits remain incompletely understood. Because adipose plays a crucial role in energy homeostasis and utilization, we hypothesized that VSG exerts its influences, in part, by modulating adipose functional states. We applied single-cell ATAC sequencing and lipid profiling to inguinal and epididymal adipose depots from mice that received sham surgery or VSG. We observed depot-specific cellular composition and chromatin accessibility patterns that were altered by VSG. Specifically, accessibility at Scd1, a fatty acid desaturase, was substantially reduced after VSG in mature adipocytes of inguinal but not epididymal depots. This was accompanied by reduced accumulation of SCD1-produced unsaturated fatty acids. Given these findings and reports that reductions in Scd1 attenuate obesity and insulin resistance and that unsaturated fatty acids stimulate glucose uptake, storage, and oxidation, our results suggest VSG exerts its beneficial effects through modifications of fatty acid profiles mediated by Scd1.

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“…The epididymis plays critical roles in sperm maturation, transport, storage, and protection by providing a suitable microenvironment [24][25][26]. The distinct segments are closely associated with the epididymal functions [27]. Male gametes leave the testis in a functionally immature status.…”

Section: Introductionmentioning

confidence: 99%

Zika virus disrupts the barrier structure and Absorption/Secretion functions of the epididymis in mice

et al. 2021

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Several studies have demonstrated that Zika virus (ZIKV) damages testis and leads to infertility in mice; however, the infection in the epididymis, another important organ of male reproductive health, has gained less attention. Previously, we detected lesions in the epididymis in interferon type I and II receptor knockout male mice during ZIKV infection. Herein, the pathogenesis of ZIKV in the epididymis was further assessed in the infected mice after footpad inoculation. ZIKV efficiently replicated in the epididymis, and principal cells were susceptible to ZIKV. ZIKV infection disrupted the histomorphology of the epididymis, and the effects were characterized by a decrease in the thickness of the epithelial layer and an increase in the luminal diameter, especially at the proximal end. Significant inflammatory cell infiltration was observed in the epididymis accompanied by an increase in the levels of interleukin (IL)-6 and IL-28. The expression of tight junction proteins was downregulated and associated with disordered arrangement of the junctions. Importantly, the expression levels of aquaporin 1 and lipocalin 8, indicators of the absorption and secretion functions of the epididymis, were markedly reduced, and the proteins were redistributed. These events synergistically altered the microenvironment for sperm maturation, disturbed sperm transport downstream, and may impact male reproductive health. Overall, these results provide new insights into the pathogenesis of the male reproductive damage caused by ZIKV infection and the possible contribution of epididymal injury into this process. Therefore, male fertility of the population in areas of ZIKV epidemic requires additional attention.

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An atlas of cell types in the mouse epididymis and vas deferens

Cited by 67 publications

References 110 publications

Spatio-temporal landscape of mouse epididymal cells and specific mitochondria-rich segments defined by large-scale single-cell RNA-seq

Spatio-temporal landscape of mouse epididymal cells and specific mitochondria-rich segments defined by large-scale single-cell RNA-seq

Single-cell Chromatin Accessibility and Lipid Profiling Reveals a Metabolic Shift in Adipocytes Induced by Bariatric Surgery

Zika virus disrupts the barrier structure and Absorption/Secretion functions of the epididymis in mice

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