Unraveling three-dimensional chromatin structural dynamics during spermatogonial differentiation

Zheng, Yi; Zhang, Lingkai; Jin, Long; Zhang, Pengfei; Li, Fuyuan; Guo, Ming; Gao, Qiang; Zeng, Yao; Li, Mingzhou

doi:10.1016/j.jbc.2021.101559

Cited by 10 publications

(10 citation statements)

References 95 publications

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“…Single-cell RNA clustering also shows three stages of spermatogonia, from SSCs to differentiating spermatogonia and then to differentiated spermatogonia. 345 These spermatogonia at different developmental stages show three-dimensional chromatin architectural differences 356 and express distinct marker genes. [343][344][345]355 For example, SSCs cluster expresses markers, including GFRA1, RET, NANOS2, NANOS3, ZBTB16, SALL4, POU3F1, FGFR3, UTF1, PAX7, UCHL1, PLZF, and ID4, differentiating spermatogonia show expression of KIT, MKI67, DMRT1, and SOHLH1, indicating the proliferation of active spermatogonia, and STRA8, KIT, and MAGE-A4 are expressed in differentiated spermatogonia.…”

Section: Adult Germline Stem Cells Spermatogonial Stem Cells For Sper...mentioning

confidence: 99%

Germline stem cells in human

Cheng

Shang

Zhou

2022

Sig Transduct Target Ther

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The germline cells are essential for the propagation of human beings, thus essential for the survival of mankind. The germline stem cells, as a unique cell type, generate various states of germ stem cells and then differentiate into specialized cells, spermatozoa and ova, for producing offspring, while self-renew to generate more stem cells. Abnormal development of germline stem cells often causes severe diseases in humans, including infertility and cancer. Primordial germ cells (PGCs) first emerge during early embryonic development, migrate into the gentile ridge, and then join in the formation of gonads. In males, they differentiate into spermatogonial stem cells, which give rise to spermatozoa via meiosis from the onset of puberty, while in females, the female germline stem cells (FGSCs) retain stemness in the ovary and initiate meiosis to generate oocytes. Primordial germ cell-like cells (PGCLCs) can be induced in vitro from embryonic stem cells or induced pluripotent stem cells. In this review, we focus on current advances in these embryonic and adult germline stem cells, and the induced PGCLCs in humans, provide an overview of molecular mechanisms underlying the development and differentiation of the germline stem cells and outline their physiological functions, pathological implications, and clinical applications.

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Section: Adult Germline Stem Cells Spermatogonial Stem Cells For Sper...mentioning

confidence: 99%

Germline stem cells in human

Cheng

Shang

Zhou

2022

Sig Transduct Target Ther

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“…Germ cells were isolated from adult Ythdf2 -ctrl and Ythdf2 cKO mice by collagenase–trypsin dissociation. Then, spermatogonia and spermatocytes were enriched with a velocity sedimentation method (STA-PUT), as previously described [27, 28].…”

Section: Methodsmentioning

confidence: 99%

“…P < 0.05 by the R packages edgeR and DESeq2. Finally, GO and KEGG analyses on DEGs were performed by using Metascape, as previously depicted [28].…”

Section: Methodsmentioning

confidence: 99%

YTHDF2 promotes DNA damage repair by positively regulating the histone methyltransferase SETDB1 in spermatogonia

Guo,

Li,

et al. 2023

Biology of Reproduction

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Genomic integrity is critical for sexual reproduction, ensuring correct transmission of parental genetic information to the descendant. To preserve genomic integrity, germ cells have evolved multiple DNA repair mechanisms, together termed DNA damage response. RNA N6-methyladenosine (m6A) is the most abundant mRNA modification in eukaryotic cells that plays important roles in DNA damage response, and YTHDF2 is a well-acknowledged m6A reader protein regulating the mRNA decay and stress response. Despite this, the correlation between YTHDF2 and DNA damage response in germ cells, if any, remains enigmatic. Here, by employing a Ythdf2-conditional knockout (cKO) mouse model as well as a Ythdf2-null GC-1 mouse spermatogonial cell line, we explored the role and the underlying mechanism for YTHDF2 in spermatogonial DNA damage response. We identified that despite no evident testicular morphological abnormalities under the normal circumstance, conditional mutation of Ythdf2 in adult male mice sensitized germ cells, including spermatogonia, to etoposide-induced DNA damage. Consistently, Ythdf2-KO GC-1 cells displayed the increased sensitivity and apoptosis in response to DNA damage, accompanied by the decreased SETDB1 (a histone methyltransferase) and H3K9me3 levels. Setdb1 knockdown in GC-1 cells generated the similar phenotype, but its overexpression in Ythdf2-null GC-1 cells alleviated the sensitivity and apoptosis in response to DNA damage. Taken together, these results demonstrate that the m6A reader YTHDF2 promotes DNA damage repair by positively regulating the histone methyltransferase SETDB1 in spermatogonia, which provides novel insights into the mechanisms underlying spermatogonial genome integrity maintenance and therefore contributes to safe reproduction.

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“…SSCs are the basis of spermatogenesis and are located at the base of the varicocele [ 94 ]. After division of the SSCs, some of the daughter cells form new SSCs, and then complete their self-renewal [ 95 ]. The other portion of the daughter cells differentiate to form Type A spermatogonia and Type B spermatogonia [ 96 ], thus allowing meiosis.…”

Section: Mfns In the Development Of Germ Cells And Embryosmentioning

confidence: 99%

Mitofusins: from mitochondria to fertility

Zhao

Heng

Wang

et al. 2022

Cell. Mol. Life Sci.

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Germ cell formation and embryonic development require ATP synthesized by mitochondria. The dynamic system of the mitochondria, and in particular, the fusion of mitochondria, are essential for the generation of energy. Mitofusin1 and mitofusin2, the homologues of Fuzzy onions in yeast and Drosophila, are critical regulators of mitochondrial fusion in mammalian cells. Since their discovery mitofusins (Mfns) have been the source of significant interest as key influencers of mitochondrial dynamics, including membrane fusion, mitochondrial distribution, and the interaction with other organelles. Emerging evidence has revealed significant insight into the role of Mfns in germ cell formation and embryonic development, as well as the high incidence of reproductive diseases such as asthenospermia, polycystic ovary syndrome, and gestational diabetes mellitus. Here, we describe the key mechanisms of Mfns in mitochondrial dynamics, focusing particularly on the role of Mfns in the regulation of mammalian fertility, including spermatogenesis, oocyte maturation, and embryonic development. We also highlight the role of Mfns in certain diseases associated with the reproductive system and their potential as therapeutic targets.

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Unraveling three-dimensional chromatin structural dynamics during spermatogonial differentiation

Cited by 10 publications

References 95 publications

Germline stem cells in human

Germline stem cells in human

YTHDF2 promotes DNA damage repair by positively regulating the histone methyltransferase SETDB1 in spermatogonia

Mitofusins: from mitochondria to fertility

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