scholarly journals Cell-fate transition and determination analysis of mouse male germ cells throughout development

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiexiang Zhao ◽  
Ping Lu ◽  
Cong Wan ◽  
Yaping Huang ◽  
Manman Cui ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Fate ◽  
Germ Cells ◽  
Transitional Cell ◽  
Critical Time ◽  
Mitotic Arrest ◽  
Cell Development ◽  
Male Germ Cell ◽  
Male Germ Cells ◽  
Germ Cell Development

AbstractMammalian male germ cell development is a stepwise cell-fate transition process; however, the full-term developmental profile of male germ cells remains undefined. Here, by interrogating the high-precision transcriptome atlas of 11,598 cells covering 28 critical time-points, we demonstrate that cell-fate transition from mitotic to post-mitotic primordial germ cells is accompanied by transcriptome-scale reconfiguration and a transitional cell state. Notch signaling pathway is essential for initiating mitotic arrest and the maintenance of male germ cells’ identities. Ablation of HELQ induces developmental arrest and abnormal transcriptome reprogramming of male germ cells, indicating the importance of cell cycle regulation for proper cell-fate transition. Finally, systematic human-mouse comparison reveals potential regulators whose deficiency contributed to human male infertility via mitotic arrest regulation. Collectively, our study provides an accurate and comprehensive transcriptome atlas of the male germline cycle and allows for an in-depth understanding of the cell-fate transition and determination underlying male germ cell development.

scholarly journals Proteomic and metabolomic analyses uncover sex-specific regulatory pathways in mouse fetal germline differentiation†

2020 ◽  
Vol 103 (4) ◽  
pp. 717-735
Author(s):  
Yohei Hayashi ◽  
Masaru Mori ◽  
Kaori Igarashi ◽  
Keiko Tanaka ◽  
Asuka Takehara ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Germ Cell ◽  
Germ Cells ◽  
Cell Development ◽  
Nucleotide Synthesis ◽  
Male Germ Cells ◽  
Regulatory Pathways ◽  
Germ Cell Development ◽  
Germ Cell Differentiation ◽  
Germline Differentiation

Abstract Regulatory mechanisms of germline differentiation have generally been explained via the function of signaling pathways, transcription factors, and epigenetic regulation; however, little is known regarding proteomic and metabolomic regulation and their contribution to germ cell development. Here, we conducted integrated proteomic and metabolomic analyses of fetal germ cells in mice on embryonic day (E)13.5 and E18.5 and demonstrate sex- and developmental stage-dependent changes in these processes. In male germ cells, RNA processing, translation, oxidative phosphorylation, and nucleotide synthesis are dominant in E13.5 and then decline until E18.5, which corresponds to the prolonged cell division and more enhanced hyper-transcription/translation in male primordial germ cells and their subsequent repression. Tricarboxylic acid cycle and one-carbon pathway are consistently upregulated in fetal male germ cells, suggesting their involvement in epigenetic changes preceding in males. Increased protein stability and oxidative phosphorylation during female germ cell differentiation suggests an upregulation of aerobic energy metabolism, which likely contributes to the proteostasis required for oocyte maturation in subsequent stages. The features elucidated in this study shed light on the unrevealed mechanisms of germ cell development.

scholarly journals CRISPR/Cas9-based genetic screen of SCNT-reprogramming resistant genes identifies critical genes for male germ cell development in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Most Sumona Akter ◽  
Masashi Hada ◽  
Daiki Shikata ◽  
Gen Watanabe ◽  
Atsuo Ogura ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Molecular Mechanisms ◽  
Essential Gene ◽  
Cell Development ◽  
Genetic Screen ◽  
Male Germ Cell ◽  
Specific Expression ◽  
Germ Cell Development ◽  
Resistant Genes

AbstractMale germ cells undergo complex developmental processes eventually producing spermatozoa through spermatogenesis, although the molecular mechanisms remain largely elusive. We have previously identified somatic cell nuclear transfer-reprogramming resistant genes (SRRGs) that are highly enriched for genes essential for spermatogenesis, although many of them remain uncharacterized in knockout (KO) mice. Here, we performed a CRISPR-based genetic screen using C57BL/6N mice for five uncharacterized SRRGs (Cox8c, Cox7b2, Tuba3a/3b, Faiml, and Gm773), together with meiosis essential gene Majin as a control. RT-qPCR analysis of mouse adult tissues revealed that the five selected SRRGs were exclusively expressed in testis. Analysis of single-cell RNA-seq datasets of adult testis revealed stage-specific expression (pre-, mid-, or post-meiotic expression) in testicular germ cells. Examination of testis morphology, histology, and sperm functions in CRISPR-injected KO adult males revealed that Cox7b2, Gm773, and Tuba3a/3b are required for the production of normal spermatozoa. Specifically, Cox7b2 KO mice produced poorly motile infertile spermatozoa, Gm773 KO mice produced motile spermatozoa with limited zona penetration abilities, and Tuba3a/3b KO mice completely lost germ cells at the early postnatal stages. Our genetic screen focusing on SRRGs efficiently identified critical genes for male germ cell development in mice, which also provides insights into human reproductive medicine.

scholarly journals Upregulated lncRNA Gm2044 inhibits male germ cell development by acting as miR-202 host gene

2019 ◽  
Vol 23 (2) ◽  
pp. 128-134 ◽  
Author(s):  
Meng Liang ◽  
Ke Hu ◽  
Chaofan He ◽  
Jinzhao Zhou ◽  
Yaping Liao
Keyword(s):  
Germ Cell ◽  
Cell Development ◽  
Host Gene ◽  
Male Germ Cell ◽  
Germ Cell Development

scholarly journals Epab and Pabpc1 Are Differentially Expressed During Male Germ Cell Development

2012 ◽  
Vol 19 (9) ◽  
pp. 911-922 ◽  
Author(s):  
Saffet Ozturk ◽  
Ozlem Guzeloglu-Kayisli ◽  
Necdet Demir ◽  
Berna Sozen ◽  
Orkan Ilbay ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Development ◽  
Differentially Expressed ◽  
Male Germ Cell ◽  
Germ Cell Development

scholarly journals Katanin-like 2 (KATNAL2) functions in multiple aspects of haploid male germ cell development in the mouse

PLoS Genetics ◽  
2017 ◽  
Vol 13 (11) ◽  
pp. e1007078 ◽  
Author(s):  
Jessica E. M. Dunleavy ◽  
Hidenobu Okuda ◽  
Anne E. O’Connor ◽  
D. Jo Merriner ◽  
Liza O’Donnell ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Development ◽  
Male Germ Cell ◽  
Germ Cell Development ◽  
Haploid Male

scholarly journals DMRTC2, PAX7, BRACHYURY/T and TERT Are Implicated in Male Germ Cell Development Following Curative Hormone Treatment for Cryptorchidism-Induced Infertility

Genes ◽  
2017 ◽  
Vol 8 (10) ◽  
pp. 267 ◽  
Author(s):  
Katharina Gegenschatz-Schmid ◽  
Gilvydas Verkauskas ◽  
Philippe Demougin ◽  
Vytautas Bilius ◽  
Darius Dasevicius ◽  
...  
Keyword(s):  
Germ Cell ◽  
Hormone Treatment ◽  
Cell Development ◽  
Male Germ Cell ◽  
Germ Cell Development

scholarly journals Disruption of Tcfap2c in Primordial Germ Cells using Prdm1-Cre Prevents Germ Cell Development

2008 ◽  
Vol 78 (Suppl_1) ◽  
pp. 64-64
Author(s):  
Jillian Guttormsen ◽  
Gerrit J. Bouma ◽  
Frances Bhushan ◽  
Trevor Williams ◽  
Quinton A. Winger
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Cell Development ◽  
Germ Cell Development

scholarly journals hnRNPH1 recruits PTBP2 and SRSF3 to cooperatively modulate alternative pre-mRNA splicing in germ cells and is essential for spermatogenesis and oogenesis

2021 ◽  
Author(s):  
Shuiqiao Yuan ◽  
Shenglei Feng ◽  
Jinmei Li ◽  
Hui Wen ◽  
Kuan Liu ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Germ Cell ◽  
Germ Cells ◽  
Rna Binding ◽  
Cell Development ◽  
Mrna Splicing ◽  
Conditional Knockout ◽  
Cell Junction ◽  
Germ Cell Development ◽  
Splicing Regulators

Abstract Coordinated regulation of alternative pre-mRNA splicing is essential for germ cell development. However, the molecular mechanism underlying that control alternative mRNA expression during germ cell development remains poorly understood. Herein, we showed that hnRNPH1, an RNA-binding protein, is highly expressed in the reproductive system and localized in the chromosomes of meiotic cells but excluded from the XY body in pachytene spermatocytes and recruits the splicing regulators PTBP2 and SRSF3 and cooperatively regulates the alternative splicing of the critical genes that are required for spermatogenesis. Conditional knockout Hnrnph1 in spermatogenic cells caused many abnormal splicing events that affect genes related to meiosis and communication between germ cells and Sertoli cells, characterized by asynapsis of chromosomes and impairment of germ-Sertoli communications, ultimately leading to male sterility. We further showed that hnRNPH1 could directly bind to SPO11 and recruit the splicing regulators PTBP2 and SRSF3 to regulate the alternative splicing of the target genes cooperatively. Strikingly, Hnrnph1 germline-specific mutant female mice were also infertile, and Hnrnph1-deficient oocytes exhibited a similar defective synapsis and cell-cell junction as shown in Hnrnph1-deficient male germ cells. Collectively, our data reveal an essential role for hnRNPH1 in regulating pre-mRNA splicing during spermatogenesis and oogenesis and support a molecular model whereby hnRNPH1 governs a network of alternative splicing events in germ cells via recruiting PTBP2 and SRSF3.

Isolation of the murine cyclin B2 cDNA and characterization of the lineage and temporal specificity of expression of the B1 and B2 cyclins during oogenesis, spermatogenesis and early embryogenesis

Development ◽  
1993 ◽  
Vol 118 (1) ◽  
pp. 229-240 ◽  
Author(s):  
D.L. Chapman ◽  
D.J. Wolgemuth
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Northern Blot ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Cell Development ◽  
Early Embryogenesis ◽  
Northern Blot Hybridization ◽  
Germ Cell Development

A cDNA encoding the murine cyclin B2 (cycB2) was isolated from an adult mouse testis cDNA library as part of studies designed to identify cyclins involved in murine germ cell development. This cycB2 cDNA was then used to examine the pattern of cycB2 expression during male and female germ cell development and in early embryogenesis, and to compare this expression with the previously characterized expression of cycB1. A single 1.7 kb cycB2 transcript was detected by northern blot hybridization analysis of total RNA isolated from midgestation embryos and various adult tissues. Northern blot and in situ hybridization analyses revealed that cycB2 expression in the testis was most abundant in the germ cells, specifically in pachytene spermatocytes. This is in contrast to the highest levels of expression of cycB1 being present in early spermatids. In situ analysis of the ovary revealed cycB2 transcripts in both germ cells and somatic cells, specifically in the oocytes and granulosa cells of growing and mature follicles. The pattern of cycB1 and cycB2 expression in ovulated and fertilized eggs was also examined. While the steady state level of cycB1 and cycB2 signal remained constant in oocytes and ovulated eggs, signal of both appeared to decrease following fertilization. In addition, both cycB1 and cycB2 transcripts were detected in the cells of the inner cell mass and the trophectoderm of the blastocyst. These results demonstrate that there are lineage- and developmental-specific differences in the pattern of the B cyclins in mammalian germ cells, in contrast to the co-expression of B cyclins in the early conceptus.

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