Expression of Cnnm1 and Its Association with Stemness, Cell Cycle, and Differentiation in Spermatogenic Cells in Mouse Testis

Chandran, Uma; Sivankutty, Indu; Kumar, Anil; Devi, Anandavalli N.; Khan, Irfan; Srivastava, Diwas; Kumar, Pradeep

doi:10.1095/biolreprod.115.130369

Cited by 14 publications

(13 citation statements)

References 45 publications

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“…GC-1spg cells, a mouse spermatogonia-derived cell line, represent the differentiation state of type B spermatogonia or preleptotene spermatocytes [1,37]. Several studies have demonstrated GC-1spg cell plasticity [1,4,78,79]. In our study, we drove BMP9 expression using a recombinant adenovirus.…”

Section: Discussionmentioning

confidence: 99%

Bone morphogenetic protein 9 induces osteogenic differentiation of germ cell 1 spermatogonial cells

Zhang

Xu²,

Chen³

et al. 2019

Preprint

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30Germ cell 1 spermatogonial (GC-1spg) cells are multipotent progenitor cells. We 31 previously confirmed that bone morphogenetic protein (BMP) 9 is among the most 32 osteogenic BMPs. However, whether GC-1spg cells are driven toward osteogenic 33 differentiation under proper stimuli is uncertain. Additionally, the molecular 34 mechanism of BMP9 remains unclear. In the present study, we aimed to determine 35 whether BMP9 can induce osteogenic differentiation of GC-1spg cells. Recombinant 36 adenoviruses were generated by the AdEasy system to regulate the BMP9 expression in 37 GC-1spg cells. We identified osteogenic markers by real-time PCR and staining 38 techniques in vitro. Ectopic ossification assays and histological analysis were also 39 performed to verify the in vivo activity of BMP9. Finally, potential signaling pathways 40 of BMP9 were assessed by transcriptome sequencing and KEGG enrichment analysis. 41Using recombinant adenoviruses, we demonstrate that BMP9 upregulates osteogenic 42 markers including Runx2, osteocalcin, osteopontin, and Sox9. BMP9 also activates 43 alkaline phosphatase activity and calcium deposition in GC-1spg cells. In vivo results 44show that BMP9 overexpression in GC-1spg cells promotes ectopic bone formation and 45 chondrogenesis. In addition, RNA-sequencing and KEGG pathway analysis 3 46 demonstrate that several signaling pathways are involved in BMP9-mediated 47 osteogenesis. GC-1spg cells not only maintain spermatogenesis but also retain the 48 ability to form bone tissue. Therefore, BMP9 activity in GC-1spg cells may help 49 identify signaling pathways implicated in bone formation and could be of use in 50 regenerative medicine. 51 Keywords: Bone morphogenetic protein 9, RNA-seq, KEGG pathway analysis, 52 recombinant adenovirus, chondrogenesis 53 Introduction 54 Germ cell 1 spermatogonial (GC-1spg) cells are mouse spermatogonia that are 55 immortalized by the SV40 large T antigen [1]. These cells can differentiate into diverse cell 56 types or undergo self-renewal, depending on different factors [2,3,4]. GC-1spg cells are 57 largely involved in spermatogenesis and have mesenchymal stem cell (MSC) differentiation 58 potential [5,6,7,8]. In other words, GC-1spg cells can differentiate into different cell types, 59including those of the osteogenic, chondrogenic, or adipogenic lineages [9,10,11,12]. 60However, several molecular events [13,14] and factors are involved in osteogenic 61 differentiation of MSCs. Importantly, bone morphogenetic proteins (BMPs) are essential for 62 this process [15,16,17]. 63 BMPs, members of the TGF-β superfamily, are required for bone formation, stem cell 64 differentiation, and male reproduction [15,16,18,19,20]. Thus far, more than 15 different 65 BMPs have been identified. Our previous work showed that BMP9 is the most osteogenic 66 BMP [21,22,23,24]. BMP9, also known as growth differentiation factor 2 (GDF-2)[25], was 67 originally isolated from the fetal mouse liver [25,26]. Bone formation involves BMP9 acting 68 through the Notch signaling ...

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Section: Discussionmentioning

confidence: 99%

Bone morphogenetic protein 9 induces osteogenic differentiation of germ cell 1 spermatogonial cells

Zhang

Xu²,

Chen³

et al. 2019

Preprint

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“…Also known as OGA, MGEA5 influences folliculogenesis [73]. Expression of Cnnm1 (cyclin M1) is associated with cell cycle and differentiation in spermatogenic cells in mouse testis [74]. Chd5 expression is restricted to post-meiotic spermatids [75].…”

Section: Several Candidate Icr Map To the Vicinity Of Genes Encoding mentioning

confidence: 99%

“…POU3F1 is involved in survival and self-renewal of mouse spermatogonial stem cells [72]. CNNM1 is produced in mouse testes from neonatal to adult stages [74]. CHD5 mediates histoneto-protamine replacement and impacts the cascade of molecular events underlying chromatin remodeling during spermatogenesis [75].…”

Section: Several Of the Candidate Icrs Map To Genes With Functions Ramentioning

confidence: 99%

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Simultaneous discovery of candidate imprinted genes and Imprinting Control Regions in the mouse genome

Bina

Wyss

2019

Preprint

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In mammals, parent-of-origin-specific gene expression is regulated by specific genomic DNA segments known as Imprinting Control Regions (ICRs) and germline Differentially Methylated Regions (gDMRs). In the mouse genome, the known ICRs/gDMRs often include clusters of a set of composite-DNA-elements known as ZFBS-morph overlaps. These elements consist of the ZFP57 binding site (ZFBS) overlapping a subset of the MLL1 morphemes. To improve detection of such clusters, we created density-plots. In genome-wide analyses, peaks in these plots pinpointed ~90% of the known ICRs/gDMRs and located candidate ICRs within relatively long genomic DNA sections. In several cases, the candidate ICRs mapped to chromatin boundaries, to a subset of gene-transcripts, or to both. By viewing the plots at the UCSC genome browser, we could examine the candidate ICRs in the context of the genes in their vicinity. This strategy uncovered several potential imprinted genes with a broad range of physiologically important functions. Examples include: folliculogenesis; lineage commitment of murine embryonic stem cells; the development of the junctional zone of the placenta; left-right patterning of the body axis; the development of the neocortex, hippocampus, and cerebellum; postnatal vision; self-renewal of mouse spermatogonial stem cells; and histone-to-protamine replacement during spermatogenesis. Predicted imprinted genes: Arid1b,

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“…It is a cell type that intermediates between type B spermatogonia and pre‐leptotene spermatocyte. It exhibited some characteristics of early spermatogonia which did not express STRA8 but could be induced to express STRA8 by RA . The HEK‐239T cell line (Human embryonic kidney cells, lentivirus‐mediated overexpressed STRA8‐GC1 spg (SGC1) and its control GC1 spg (CGC1) were derived in our laboratory.…”

Section: Methodsmentioning

confidence: 99%

Meiotic gatekeeper STRA8 regulates cell cycle by interacting with SETD8 during spermatogenesis

Niu

Guo

Shen

et al. 2020

J Cellular Molecular Medi

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STRA8 (Stimulated By Retinoic Acid Gene 8) is a retinoic acid (RA) induced gene that plays vital roles in spermatogonial proliferation, differentiation and meiosis. The SETD8 and STRA8 protein interaction was discovered using the yeast two‐hybrid technique using a mouse spermatogonial stem cell (SSC) cDNA library. The interaction of these two proteins was confirmed using co‐immunoprecipitation and identification of key domains governing the protein: protein complex. STRA8 and SETD8 showed a mutual transcriptional regulation pattern that provided evidence that SETD8 negatively regulated transcriptional activity of the STRA8 promoter. The SETD8 protein directly bound to the proximal promoter of the STRA8 gene. STRA8 increased the transcriptional activity of SETD8 promoter in a dose‐dependent manner. For the first time, we have discovered that STRA8 and SETD8 display a cell cycle‐dependent expression pattern in germline cells. Expression levels of SETD8 and H4K20me1 in S phase of STRA8 overexpression GC1 cells were different from that previously observed in tumour cell lines. In wild‐type mice testis, SETD8, H4K20me1 and PCNA co‐localized with STRA8 in spermatogonia. Further, our studies quantitated abnormal expression levels of cell cycle and ubiquitination‐related factors in STRA8 dynamic models. STRA8 and SETD8 may regulate spermatogenesis via Cdl4‐Clu4A‐Ddb1 ubiquitinated degradation axis in a PCNA‐dependent manner.

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Expression of Cnnm1 and Its Association with Stemness, Cell Cycle, and Differentiation in Spermatogenic Cells in Mouse Testis

Cited by 14 publications

References 45 publications

Bone morphogenetic protein 9 induces osteogenic differentiation of germ cell 1 spermatogonial cells

Bone morphogenetic protein 9 induces osteogenic differentiation of germ cell 1 spermatogonial cells

Simultaneous discovery of candidate imprinted genes and Imprinting Control Regions in the mouse genome

Meiotic gatekeeper STRA8 regulates cell cycle by interacting with SETD8 during spermatogenesis

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