GSK-3 promotes S-phase entry and progression in <i>C. elegans</i> germline stem cells to maintain tissue output

Furuta, Tokiko; Joo, Hyoe Jin; Trimmer, Kenneth A.; Chen, Shin-Yu; Arur, Swathi

doi:10.1242/dev.161042

Cited by 14 publications

(15 citation statements)

References 69 publications

(82 reference statements)

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“…The size increase and number reduction were less pronounced in smrc-1 nuclei, although still significant (Fig 8A). To investigate if smrc-1 mutants were resistant to mitotic arrest, we repeated the HU treatment and performed anti-H3S10phos (histone H3 phosphorylated on serine 10) labeling to detect mitotic nuclei [75]. Untreated wildtype and smrc-1(om138) mutants had the same mitotic index, whereas HU-treated smrc-1 mutants had a significantly higher mitotic index than HU-treated wildtype controls (Fig 8B).…”

Section: Resultsmentioning

confidence: 99%

A DNA repair protein and histone methyltransferase interact to promote genome stability in the Caenorhabditis elegans germ line

Yang¹,

Xu²,

Russell³

et al. 2019

PLoS Genet

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Histone modifications regulate gene expression and chromosomal events, yet how histone-modifying enzymes are targeted is poorly understood. Here we report that a conserved DNA repair protein, SMRC-1, associates with MET-2, the C . elegans histone methyltransferase responsible for H3K9me1 and me2 deposition. We used molecular, genetic, and biochemical methods to investigate the biological role of SMRC-1 and to explore its relationship with MET-2. SMRC-1, like its mammalian ortholog SMARCAL1, provides protection from DNA replication stress. SMRC-1 limits accumulation of DNA damage and promotes germline and embryonic viability. MET-2 and SMRC-1 localize to mitotic and meiotic germline nuclei, and SMRC-1 promotes an increase in MET-2 abundance in mitotic germline nuclei upon replication stress. In the absence of SMRC-1, germline H3K9me2 generally decreases after multiple generations at high culture temperature. Genetic data are consistent with MET-2 and SMRC-1 functioning together to limit replication stress in the germ line and in parallel to promote other germline processes. We hypothesize that loss of SMRC-1 activity causes chronic replication stress, in part because of insufficient recruitment of MET-2 to nuclei.

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Section: Resultsmentioning

confidence: 99%

A DNA repair protein and histone methyltransferase interact to promote genome stability in the Caenorhabditis elegans germ line

Yang¹,

Xu²,

Russell³

et al. 2019

PLoS Genet

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“…S6D). Soaking day 5 animals in a solution of 500 μM EdU in M9, as described by Furuta et al (2018), also resulted in a subpopulation that completely lacked EdU labeling. As the duration of EdU feeding increased, so did the proportion of animals showing labeling.…”

Section: Edu Labeling Experimentsmentioning

confidence: 97%

Rapid, population-wide declines in stem cell number and activity during reproductive aging inC. elegans

2019

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C. elegans hermaphrodites display dramatic age-related decline of reproduction early in life, while somatic functions are still robust. To understand reproductive aging, we analyzed the assembly line of oocyte production that generates fertilized eggs. Aging germlines displayed both sporadic and population-wide changes. A small fraction of aging animals displayed endomitotic oocytes in the germline and other defects. By contrast, all animals displayed age-related decreases in germline size and function. As early as day 3 of adulthood, animals displayed fewer stem cells and a slower cell cycle, which combine to substantially decrease progenitor zone output. The C. elegans germline is the only adult tissue that contains stem cells, allowing the analysis of stem cells in aging. To investigate the mechanism of the decrease in stem cell number, we analyzed the Notch signaling pathway. The Notch effectors LST-1 and SYGL-1 displayed agerelated decreases in expression domains, suggesting a role for Notch signaling in germline aging. The results indicate that although sporadic defects account for the sterility of some animals, population-wide changes account for the overall pattern of reproductive aging.

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“…CDK-2/CYE-1 is required for germline mitotic cell cycling, but CYE-1 accumulation is not cell cycle-regulated, unlike in somatic cells where CYE-1 expression is limited to late G1 and S phase. Glycogen synthase kinase ortholog GSK-3 is required for high CDK-2 expression throughout the cell cycle, promoting rapid cell cycling (Furuta et al 2018). Multiple environmental conditions that result in mitotic cell cycle quiescence all result in a G2 arrest (see below).…”

Section: Adult Germline Stem Cell System: Organization and Cell Biologymentioning

confidence: 99%

Biology of the Caenorhabditis elegans Germline Stem Cell System

2019

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Stem cell systems regulate tissue development and maintenance. The germline stem cell system is essential for animal reproduction, controlling both the timing and number of progeny through its influence on gamete production. In this review, we first draw general comparisons to stem cell systems in other organisms, and then present our current understanding of the germline stem cell system in Caenorhabditis elegans. In contrast to stereotypic somatic development and cell number stasis of adult somatic cells in C. elegans, the germline stem cell system has a variable division pattern, and the system differs between larval development, early adult peak reproduction and age-related decline. We discuss the cell and developmental biology of the stem cell system and the Notch regulated genetic network that controls the key decision between the stem cell fate and meiotic development, as it occurs under optimal laboratory conditions in adult and larval stages. We then discuss alterations of the stem cell system in response to environmental perturbations and aging. A recurring distinction is between processes that control stem cell fate and those that control cell cycle regulation. C. elegans is a powerful model for understanding germline stem cells and stem cell biology.

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GSK-3 promotes S-phase entry and progression in C. elegans germline stem cells to maintain tissue output

Cited by 14 publications

References 69 publications

A DNA repair protein and histone methyltransferase interact to promote genome stability in the Caenorhabditis elegans germ line

A DNA repair protein and histone methyltransferase interact to promote genome stability in the Caenorhabditis elegans germ line

Rapid, population-wide declines in stem cell number and activity during reproductive aging inC. elegans

Biology of the Caenorhabditis elegans Germline Stem Cell System

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