Constitutive activation of CTNNB1 results in a loss of spermatogonial stem cell activity in mice

Boyer, Alexandre; Zhang, Xiangfan; Levasseur, Adrien; Nader, Nour Abou; St-Jean, G; Nagano, Makoto; Boerboom, Derek

doi:10.1371/journal.pone.0251911

Cited by 15 publications

(10 citation statements)

References 61 publications

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“…Among these, 23 mitosisrelated proteins were used to establish the PPI network by using Cytoscape and three genes in the PPI network were identified as hub genes, including CTNNB1, CUL4B, and RUVBL1. For instance, a recent study revealed that CTNNB1 is an essential regulator of murine spermatogonial stem cell fate to induce its differentiation into spermatogonia (35). In this study, we found that decreases in mRNA and protein levels of CTNNB1 with increasing age, suggestive of its importance for the early stages of Tibetan sheep spermatogenesis.…”

Section: Discussionsupporting

confidence: 58%

Proteome Informatics in Tibetan Sheep (Ovis aries) Testes Suggest the Crucial Proteins Related to Development and Functionality

Luo

et al. 2022

Front. Vet. Sci.

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Testis has an indispensable function in male reproduction of domestic animals. Tibetan sheep (Ovis aries) is a locally adapted breed of sheep raised in the Qinghai-Tibet Plateau, with outsized roles in providing the livelihood for millions of residents. Nevertheless, less is known on how protein expression and their functional roles in developmental testes of such breed limit their use in breeding efforts. In this study, we obtained comprehensive protein profiles from testes of Tibetan sheep at three developmental stages (including pre-puberty, post-puberty, and adulthood) using data-independent acquisition-based proteomic strategy to quantitatively identify the differentially abundant proteins (DAPs) associated with testicular development and function and to unravel the molecular basis of spermatogenesis. A total of 6,221 proteins were differentially expressed in an age-dependent manner. The reliability of the gene expression abundance was corroborated by quantitative PCR and targeted parallel reaction monitoring. These DAPs were significantly enriched to biological processes concerning spermatid development and sperm deformation, mitosis, glycolytic process, cell-cell/extracellular matrix (ECM) junctions, cell proliferation, apoptosis, and migration and to the pathways including, developmental process and sexual reproduction-related (such as VEGF, estrogen, insulin, GnRH, Hippo, PI3K-Akt, mTOR, MAPK, and AMPK), and testicular cell events-related pathways (such as tight/gap/adherens junctions, ECM-receptor interaction, regulation of actin cytoskeleton, glycolysis, cell cycle, and meiosis). Based on these bioinformatics analysis, we constructed four protein–protein interaction network, among which the proteins are involved in mitosis, meiosis, spermiogenesis, and testicular microenvironment, respectively. Altogether, these bioinformatics-based sequencing results suggest that many protein-coding genes were expressed in a development-dependent manner in Tibetan sheep testes to contribute to the testicular cell development and their surrounding microenvironment remodeling at various stages of spermatogenesis. These findings have important implications for further understanding of the mechanisms underlying spermatogenesis in sheep and even other plateau-adapted animals.

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Section: Discussionsupporting

confidence: 58%

Proteome Informatics in Tibetan Sheep (Ovis aries) Testes Suggest the Crucial Proteins Related to Development and Functionality

Luo

et al. 2022

Front. Vet. Sci.

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“…A subsequent study using a Ctnnb1 tm1Mmt/tm1Mmt ; Ddx4 cre/+ model showed that the constitutive activation of β-catenin in fetal gonocytes triggered SSC proliferation and spermatocyte depletion 53 . However, using the Ctnnb1 tm1Mmt/tm1Mmt ; Ddx4 cre/+ model, Boyer et al ., found that the constitutive activation of β-catenin in fetal gonocytes compromised SSCs activity and promoted SSCs differentiation 54 . In addition, the constitutive activation of β-catenin in fetal gonocytes using a Ctnnb1 tm1Mmt/tm1Mmt ; Nanos3 cre/+ model reduced the GFRα1 + SSC pool 55 .…”

Section: Discussionmentioning

confidence: 99%

BMI1 promotes spermatogonial stem cell maintenance by epigenetically repressing Wnt10b/β-catenin signaling

Yu¹,

Shen²,

Lin³

et al. 2022

Int. J. Biol. Sci.

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The self-renewal of spermatogonial stem cells (SSCs) requires a special microenvironment and is strictly controlled. Previously, we identified BMI1 as a key regulator of spermatogenesis in a knock-out mouse model. However, the mechanisms by which BMI1 regulates SSC maintenance remain largely unknown. Herein, we show that BMI1 is essential for SSC maintenance. BMI1 directs the transcriptional repression of target genes by increasing H2AK119ub and reducing H3K4me3 in SSCs. Furthermore, BMI1 inhibition resulted in the transcriptional activation of Wnt10b and thereby promoted the nuclear translocation of β-catenin in SSCs. Importantly, the suppression of Wnt/β-catenin signaling restored both the cytoplasmic expression of β-catenin and SSC maintenance in BMI1-deficient SSCs. Finally, we demonstrated that Wnt/β-catenin signaling was also involved in BMI1-mediated SSC maintenance in vivo . Altogether, our study not only reveals a novel mechanism for BMI1 in the process of SSC maintenance, but also provides a potential new strategy for treating male infertility.

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“…Catenin beta-1; WNT binds CTNNB1 pathway mediates proliferation of progenitor cells and spermatogonial stem cells in spermatogenesis process. [11] Lgals3 Galectin-3; Galactose-specific lectin which binds IgE. May mediate with alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cell migration.…”

Section: Ctnnb1mentioning

confidence: 99%

“…Vimentin is an intermediate filament that extends from the nuclear periphery to the cell membrane, and is connected with the tubulin and actin cytoskeleton [10]. The cellular functions of vimentin contribute to cellular stiffness, actin position, cell migration, cell division, and organelle organization in different stages of spermatogenesis [10,11]. In addition, vimentin plays other vital roles, such as determining cell shape, cell differentiation, cell motility, maintaining cell junctions, assisting in keeping ordinary spermatogonia morphology, and playing a main role in anchoring differentiating germ cells to the seminiferous epithelium [12,13].…”

Section: Introductionmentioning

confidence: 99%

Testicular Localization and Potential Function of Vimentin Positive Cells during Spermatogonial Differentiation Stages

Tabar

Azizi

Karoii

et al. 2022

Animals

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Vimentin is a type of intermediate filament (IF) and one of the first filaments expressed in spermatogenesis. Vimentin plays numerous roles, consisting of the determination of cell shape, differentiation, cell motility, the maintenance of cell junctions, intracellular trafficking, and assisting in keeping normal differentiating germ cell morphology. This study investigated the vimentin expression in two populations of undifferentiated and differentiated spermatogonia. We examined vimentin expression in vivo and in vitro by immunocytochemistry (ICC), immunohistochemistry (IMH), and Fluidigm real-time polymerase chain reaction. IMH data showed that the high vimentin expression was localized in the middle of seminiferous tubules, and low expression was in the basal membrane. ICC analysis of the colonies by isolated differentiated spermatogonia indicated the positive expression for the vimentin antibody, but vimentin’s expression level in the undifferentiated population was negative under in vitro conditions. Fluidigm real-time PCR analysis showed significant vimentin expression in differentiated spermatogonia compared to undifferentiated spermatogonia (p < 0.05). Our results showed that vimentin is upregulated in the differentiation stages of spermatogenesis, proving that vimentin is an intermediate filament with crucial roles in the differentiation stages of testicular germ cells. These results support the advanced investigations of the spermatogenic process, both in vitro and in vivo.

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Constitutive activation of CTNNB1 results in a loss of spermatogonial stem cell activity in mice

Cited by 15 publications

References 61 publications

Proteome Informatics in Tibetan Sheep (Ovis aries) Testes Suggest the Crucial Proteins Related to Development and Functionality

Proteome Informatics in Tibetan Sheep (Ovis aries) Testes Suggest the Crucial Proteins Related to Development and Functionality

BMI1 promotes spermatogonial stem cell maintenance by epigenetically repressing Wnt10b/β-catenin signaling

Testicular Localization and Potential Function of Vimentin Positive Cells during Spermatogonial Differentiation Stages

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