19
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Single-cell RNA-seq uncovers dynamic processes and critical regulators in mouse spermatogenesis

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          A systematic interrogation of male germ cells is key to complete understanding of molecular mechanisms governing spermatogenesis and the development of new strategies for infertility therapies and male contraception. Here we develop an approach to purify all types of homogeneous spermatogenic cells by combining transgenic labeling and synchronization of the cycle of the seminiferous epithelium, and subsequent single-cell RNA-sequencing. We reveal extensive and previously uncharacterized dynamic processes and molecular signatures in gene expression, as well as specific patterns of alternative splicing, and novel regulators for specific stages of male germ cell development. Our transcriptomics analyses led us to discover discriminative markers for isolating round spermatids at specific stages, and different embryo developmental potentials between early and late stage spermatids, providing evidence that maturation of round spermatids impacts on embryo development. This work provides valuable insights into mammalian spermatogenesis, and a comprehensive resource for future studies towards the complete elucidation of gametogenesis.

          Related collections

          Most cited references58

          • Record: found
          • Abstract: found
          • Article: not found

          Recombination, Pairing, and Synapsis of Homologs during Meiosis.

          Recombination is a prominent feature of meiosis in which it plays an important role in increasing genetic diversity during inheritance. Additionally, in most organisms, recombination also plays mechanical roles in chromosomal processes, most notably to mediate pairing of homologous chromosomes during prophase and, ultimately, to ensure regular segregation of homologous chromosomes when they separate at the first meiotic division. Recombinational interactions are also subject to important spatial patterning at both early and late stages. Recombination-mediated processes occur in physical and functional linkage with meiotic axial chromosome structure, with interplay in both directions, before, during, and after formation and dissolution of the synaptonemal complex (SC), a highly conserved meiosis-specific structure that links homolog axes along their lengths. These diverse processes also are integrated with recombination-independent interactions between homologous chromosomes, nonhomology-based chromosome couplings/clusterings, and diverse types of chromosome movement. This review provides an overview of these diverse processes and their interrelationships.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            A highly conserved program of neuronal microexons is misregulated in autistic brains.

            Alternative splicing (AS) generates vast transcriptomic and proteomic complexity. However, which of the myriad of detected AS events provide important biological functions is not well understood. Here, we define the largest program of functionally coordinated, neural-regulated AS described to date in mammals. Relative to all other types of AS within this program, 3-15 nucleotide "microexons" display the most striking evolutionary conservation and switch-like regulation. These microexons modulate the function of interaction domains of proteins involved in neurogenesis. Most neural microexons are regulated by the neuronal-specific splicing factor nSR100/SRRM4, through its binding to adjacent intronic enhancer motifs. Neural microexons are frequently misregulated in the brains of individuals with autism spectrum disorder, and this misregulation is associated with reduced levels of nSR100. The results thus reveal a highly conserved program of dynamic microexon regulation associated with the remodeling of protein-interaction networks during neurogenesis, the misregulation of which is linked to autism.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found
              Is Open Access

              Cellular source and mechanisms of high transcriptome complexity in the mammalian testis.

              Understanding the extent of genomic transcription and its functional relevance is a central goal in genomics research. However, detailed genome-wide investigations of transcriptome complexity in major mammalian organs have been scarce. Here, using extensive RNA-seq data, we show that transcription of the genome is substantially more widespread in the testis than in other organs across representative mammals. Furthermore, we reveal that meiotic spermatocytes and especially postmeiotic round spermatids have remarkably diverse transcriptomes, which explains the high transcriptome complexity of the testis as a whole. The widespread transcriptional activity in spermatocytes and spermatids encompasses protein-coding and long noncoding RNA genes but also poorly conserves intergenic sequences, suggesting that it may not be of immediate functional relevance. Rather, our analyses of genome-wide epigenetic data suggest that this prevalent transcription, which most likely promoted the birth of new genes during evolution, is facilitated by an overall permissive chromatin in these germ cells that results from extensive chromatin remodeling. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.
                Bookmark

                Author and article information

                Contributors
                jsli@sibcb.ac.cn
                tangfuchou@pku.edu.cn
                minghan@sibcb.ac.cn
                Journal
                Cell Res
                Cell Res
                Cell Research
                Nature Publishing Group UK (London )
                1001-0602
                1748-7838
                30 July 2018
                30 July 2018
                September 2018
                : 28
                : 9
                : 879-896
                Affiliations
                [1 ]ISNI 0000 0004 1797 8419, GRID grid.410726.6, State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, , University of Chinese Academy of Sciences, ; Shanghai, 200031 China
                [2 ]ISNI 0000 0001 2256 9319, GRID grid.11135.37, Beijing Advanced Innovation Center for Genomics, Biomedical Institute for Pioneering Investigation via Convergence, College of Life Sciences, , Peking University, ; Beijing, 100871 China
                [3 ]ISNI 0000 0004 0369 313X, GRID grid.419897.a, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, ; Beijing, 100871 China
                [4 ]ISNI 0000 0001 2256 9319, GRID grid.11135.37, Peking-Tsinghua Center for Life Sciences, , Peking University, ; Beijing, 100871 China
                [5 ]ISNI 0000 0000 9255 8984, GRID grid.89957.3a, State Key Laboratory of Reproductive Medicine, , Nanjing Medical University, ; Nanjing, Jiangsu 211166 China
                [6 ]ISNI 0000 0001 2157 6568, GRID grid.30064.31, School of Molecular Biosciences and the Center for Reproductive Biology, , Washington State University, ; Pullman, WA USA
                Author information
                http://orcid.org/0000-0002-8625-7717
                Article
                74
                10.1038/s41422-018-0074-y
                6123400
                30061742
                08749b74-9e58-40c0-9d44-f032a97a52ad
                © IBCB, SIBS, CAS 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 15 June 2018
                : 25 June 2018
                : 5 July 2018
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 31471401
                Award ID: 31671553
                Award ID: 31571536
                Award ID: 31625018
                Award Recipient :
                Categories
                Article
                Custom metadata
                © IBCB, SIBS, CAS 2018

                Cell biology
                Cell biology

                Comments

                Comment on this article