Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY, United States.
Department of Zoology, School of Biological Sciences, Central University of Kerala, Kasargod, Kerala, India.
Front Endocrinol (Lausanne). 2024 Jul 11;15:1394812. doi: 10.3389/fendo.2024.1394812. eCollection 2024.
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.
精子发生是一个多步骤的生物学过程，有丝分裂活跃的二倍体（2n）精原细胞通过有丝分裂编程分化为单倍体（n）精子。在过去十年中，男性不育症的惊人上升已成为全球关注的问题，因此需要广泛分析睾丸基因表达。下一代测序（NGS）技术的进步彻底改变了我们对包括精子发生在内的复杂生物学事件的认识。然而，尽管过去曾多次尝试使用批量组织或单细胞水平来揭示睾丸转录特征，但关于睾丸转录组学和相关疾病的综合综述却很有限。值得注意的是，阐明精子发生各个阶段全基因组基因表达模式的技术提供了睾丸转录的动态分子景观。我们的综述讨论了单细胞 RNA 测序（Sc-RNA-seq）相对于批量 RNA-seq 在睾丸组织中的优势。此外，我们强调了细胞异质性、空间转录组学、动态基因表达以及睾丸内不同细胞群体（包括生殖细胞（Gc）、支持细胞（Sc）、小管周细胞（PTc）、间质细胞（Lc）等）之间的细胞间相互作用。此外，我们总结了单细胞转录组学研究的关键发现，这些发现揭示了睾丸疾病和男性不育症中涉及的发育机制。这些见解强调了 Sc-RNA-seq 在推进我们对睾丸转录景观的认识方面的关键作用，并可能成为制定未来男性生殖健康临床干预措施的潜在资源。
