Epigenetic regulation of drosophila germline stem cell maintenance and differentiation

Vidaurre, Velinda; Chen, Xin

doi:10.1016/j.ydbio.2021.02.003

Cited by 19 publications

(20 citation statements)

References 210 publications

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“…At the apical end of each ovariole lies the germarium, containing the stem cell niche at its anterior tip ( figure 1 a ). The stem cell niche is made of 2 to 3 GSCs and supporting cap and terminal filament cells [ 25 , 26 ]. Female GSCs undergo ACD to generate two daughter cells: a GSC to renew the stem cell pool and a differentiating daughter cell, called the cystoblast (CB), both supported by escort cells.…”

Section: Drosophila Female Germline Stem and Daughter Cellsmentioning

confidence: 99%

“…The Drosophila adult male gonad comprises two spiral-shaped testes, each with the GSC niche located at its apical end ( figure 2 a ). Each Drosophila testis hosts 6–15 GSCs surrounding 10–15 non-dividing stromal cells, which form the hub region, organized by cell-cell adhesion molecules such as integrins and cadherins [ 4 , 25 , 26 ]. The number of GSCs can vary between different fly strains [ 4 ].…”

Section: Drosophila Male Germline Stem and Daughter Cellsmentioning

confidence: 99%

“…Furthermore in males, Gbb/Dpp signalling from both the hub and CySCs activate BMP, leading to bam repression in GSCs [ 44 ]. Another difference is that each female niche hosts 2 to 3 GSCs, while males are more complex, hosting up to 15 GSCs per niche [ 4 , 25 , 26 ]. The differential mechanism of spindle orientation in male GSCs [ 75 ], which has not been observed in females, might be necessary due to this larger niche.…”

Section: Future Perspectivesmentioning

confidence: 99%

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Centromere function in asymmetric cell division in Drosophila female and male germline stem cells

2021

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The centromere is the constricted chromosomal region required for the correct separation of the genetic material at cell division. The kinetochore protein complex assembles at the centromere and captures microtubules emanating from the centrosome to orchestrate chromosome segregation in mitosis and meiosis. Asymmetric cell division (ACD) is a special type of mitosis that generates two daughter cells with different fates. Epigenetic mechanisms operating at the centromere have been proposed to contribute to ACD. Recent studies have shown that an asymmetric distribution of CENP-A—the centromere-specific histone H3 variant—between sister chromatids can bias chromosome segregation in ACD. In stem cells, this leads to non-random sister chromatid segregation, which can affect cell fate. These findings support the ‘silent sister' hypothesis, according to which the mechanisms of ACD are epigenetically regulated through centromeres. Here, we review the recent data implicating centromeres in ACDs and cell fate in Drosophila melanogaster female and male germline stem cells.

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Section: Drosophila Female Germline Stem and Daughter Cellsmentioning

confidence: 99%

Section: Drosophila Male Germline Stem and Daughter Cellsmentioning

confidence: 99%

Section: Future Perspectivesmentioning

confidence: 99%

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Centromere function in asymmetric cell division in Drosophila female and male germline stem cells

2021

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“…In addition to the regulation of protein turnover and translational repression, the epigenetic control of transcription is also involved in switching from the stem cell fate to the differentiated state [26,27] Epigenetic mechanisms include structural changes of the chromatin or recruitment of transcription regulators, which prevent the ectopic expression of germline differentiation genes in GSCs or activate them in pre-CBs and CBs.…”

Section: Introductionmentioning

confidence: 99%

Drosophila MESR4 Gene Ensures Germline Stem Cell Differentiation by Promoting the Transcription of bag of marbles

Szarka-Kovács

Takács

Bence

et al. 2022

Cells

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Ovarian germline stem cells (GSCs) of Drosophila melanogaster provide a valuable in vivo model to investigate how the adult stem cell identity is maintained and the differentiation of the daughter cells is regulated. GSCs are embedded into a specialized cellular microenvironment, the so-called stem cell niche. Besides the complex signaling interactions between the germ cells and the niche cells, the germ cell intrinsic mechanisms, such as chromatin regulation and transcriptional control, are also crucial in the decision about self-renewal and differentiation. The key differentiation regulator gene is the bag of marbles (bam), which is transcriptionally repressed in the GSCs and de-repressed in the differentiating daughter cell. Here, we show that the transcription factor MESR4 functions in the germline to promote GSC daughter differentiation. We find that the loss of MESR4 results in the accumulation of GSC daughter cells which fail to transit from the pre-cystoblast (pre-CB) to the differentiated cystoblast (CB) stage. The forced expression of bam can rescue this differentiation defect. By a series of epistasis experiments and a transcriptional analysis, we demonstrate that MESR4 positively regulates the transcription of bam. Our results suggest that lack of repression alone is not sufficient, but MESR4-mediated transcriptional activation is also required for bam expression.

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“…GBs first go through a transit-amplifying stage with four rounds of mitosis as spermatogonial cells (SGs). Once spermatogonial proliferation is complete, cells enter the spermatocyte stage when they initiate a robust gene expression program and epigenomic changes to prepare for meiotic divisions and spermatid differentiation [25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Roles of the distinct N-terminal amino acid between H3 and H3.3 in Drosophila male germline stem cell lineage

Chandrasekhara

Ranjan

Urban

et al. 2022

Preprint

Self Cite

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Adult stem cells undergo asymmetric cell divisions to produce two daughter cells with distinct cell fates: one capable of self-renewal and the other committed for differentiation. Mis-regulation of this delicate balance can lead to cancer and tissue degeneration. During asymmetric division of Drosophila male germline stem cells (GSCs), preexisting (old) and newly synthesized histone H3 are differentially segregated whereas old and new histone variant H3.3 are more equally inherited. However, what underlies these distinct inheritance patterns remains unknown. Here, we report that the N-terminal tails of H3 and H3.3 are critical for their inheritance patterns, as well as GSC maintenance and proper differentiation. H3 and H3.3 differ at the 31st position in their N-termini with Alanine for H3 and Serine for H3.3. By swapping these two amino acids, we generated two mutant histones (i.e., H3A31S and H3.3S31A). Upon expressing them in the early-stage germline, we identified opposing phenotypes: over-population of early-stage germ cells in the H3A31S-expressing testes and significant germ cell loss in testes expressing the H3.3S31A. Asymmetric H3 inheritance is disrupted in the H3A31S-expressing GSCs, due to mis-incorporation of old histones between sister chromatids during DNA replication. Furthermore, H3.3S31A mutation accelerates old histone turn-over in the GSCs. Finally, using a modified Chromatin Immunocleavage assay on early-stage germ cells, we found that H3A31S has an enhanced occupancy at the promoters and transcription starting sites than H3, while H3.3S31A is more enriched at transcriptionally silent intergenic regions compared to H3.3. Overall, these results suggest that the 31st amino acids for both H3 and H3.3 are critical for their proper genomic occupancy and function. Together, our findings indicate a critical role for the different amino acid composition of the N-terminal tails between H3 and H3.3 in an endogenous stem cell lineage, and provide insights into the importance of proper histone inheritance in specifying cell fates and regulating cellular differentiation.

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Epigenetic regulation of drosophila germline stem cell maintenance and differentiation

Cited by 19 publications

References 210 publications

Centromere function in asymmetric cell division in Drosophila female and male germline stem cells

Centromere function in asymmetric cell division in Drosophila female and male germline stem cells

Drosophila MESR4 Gene Ensures Germline Stem Cell Differentiation by Promoting the Transcription of bag of marbles

Roles of the distinct N-terminal amino acid between H3 and H3.3 in Drosophila male germline stem cell lineage

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