A sensitized genetic screen to identify regulators of <i>Caenorhabditis elegans</i> germline stem cells

Robinson-Thiewes, Sarah; Kershner, Aaron M.; Shin, Heaji; Haupt, Kimberly A.; Kroll-Connor, Peggy; Kimble, Judith

doi:10.1093/g3journal/jkab439

“…Subunits of the DNA polymerase alpha–primase complex: Yoon et al found that DIV-1 (regulatory subunit) is indispensable for GLP-1/Notch-mediated germ cell proliferation during early larval development, whereas POLA-1 (catalytic subunit) and two primase subunits, PRI-1 and PRI-2, play a crucial role in GLP-1/Notch-mediated maintenance of proliferative cell fate during adulthood [ 17 ]. Robinson-Thiewes et al also identified POLE-1 (the catalytic subunit of DNA polymerase e) as a regulator of germ cell proliferation [ 18 ].…”

Section: Glp-1/notch-activation-mediated Tumorigenesis: Ectopic Proli...mentioning

confidence: 99%

C. elegans Germline as Three Distinct Tumor Models

Jones,

Norman,

Tiet

et al. 2024

Biology

0

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Tumor cells display abnormal growth and division, avoiding the natural process of cell death. These cells can be benign (non-cancerous growth) or malignant (cancerous growth). Over the past few decades, numerous in vitro or in vivo tumor models have been employed to understand the molecular mechanisms associated with tumorigenesis in diverse regards. However, our comprehension of how non-tumor cells transform into tumor cells at molecular and cellular levels remains incomplete. The nematode C. elegans has emerged as an excellent model organism for exploring various phenomena, including tumorigenesis. Although C. elegans does not naturally develop cancer, it serves as a valuable platform for identifying oncogenes and the underlying mechanisms within a live organism. In this review, we describe three distinct germline tumor models in C. elegans, highlighting their associated mechanisms and related regulators: (1) ectopic proliferation due to aberrant activation of GLP-1/Notch signaling, (2) meiotic entry failure resulting from the loss of GLD-1/STAR RNA-binding protein, (3) spermatogenic dedifferentiation caused by the loss of PUF-8/PUF RNA-binding protein. Each model requires the mutations of specific genes (glp-1, gld-1, and puf-8) and operates through distinct molecular mechanisms. Despite these differences in the origins of tumorigenesis, the internal regulatory networks within each tumor model display shared features. Given the conservation of many of the regulators implicated in C. elegans tumorigenesis, it is proposed that these unique models hold significant potential for enhancing our comprehension of the broader control mechanisms governing tumorigenesis.

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“…Yoon et al found that DIV-1 (regulatory subunit) is indispensable for GLP-1/Notch-mediated germ cell proliferation during early larval development, whereas POLA-1 (catalytic subunit) and two primase subunits, PRI-1 and PRI-2, play a crucial role in GLP-1/Notch-mediated maintenance of proliferative cell fate during adulthood[16]. Robinson-Thiewes et al also identified POLE-1 (the catalytic subunit of DNA polymerase e) as a regulator of germ cell proliferation[17].…”

mentioning

confidence: 99%

C. elegans Germline as Three Distinct Tumor Models

Jones,

Norman,

Tiet

et al. 2024

Preprint

0

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Tumor cells display abnormal growth and division, avoiding the natural process of cell death. These cells can be benign (non-cancerous growth) or malignant (cancerous growth). Over the past few decades, numerous in vitro or in vivo tumor models have been employed to understand the molecular mechanisms associated with tumorigenesis in diverse aspects. However, our comprehension of how non-tumor cells transform into tumor cells at molecular and cellular levels remains incomplete. The nematode C. elegans has emerged as an excellent model organism for exploring various phenomena, including tumorigenesis. Although C. elegans does not naturally develop cancer, it serves as a valuable platform for identifying oncogenes and the underlying mechanisms within a live organism. In this review, we describe three distinct germline tumor models in C. elegans, highlighting their associated mechanisms and related regulators. Given the conservation of many of the regulators implicated in C. elegans tumorigenesis, it is proposed that these unique models hold significant potential for enhancing our comprehension of the broader control mechanisms governing tumorigenesis.

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Analysis of Notch1 signaling in mammalian sperm development

Sambe

¹

,

Yoshihara

²

,

Nishino

³

et al. 2023

BMC Res Notes

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Objective A mammalian Delta-Notch signaling component, Notch1, has been suggested for its expression during the normal sperm development although its conditional deletion caused no apparent abnormalities. Since we established our original transgenic mouse system that enabled labeling of past and ongoing Notch1 signaling at a cellular level, we tried to validate that observation in vivo. Our transgenic mouse system used Cre/loxP system to induce tandem dsRed expression upon Notch1 signaling. Results To our surprise, we were unable to observe tandem dsRed expression in the seminiferous tubules where the sperms developed. In addition, tandem dsRed expression was lacking in the somatic cells of the next generation in our transgenic mouse system, suggesting that sperms received no Notch1 signaling during their development. To validate this result, we conducted re-analysis of four single-cell RNA-seq datasets from mouse and human testes and showed that Notch1 expression was little in the sperm cell lineage. Collectively, our results posed a question into the involvement of Notch1 in the normal sperm development although this observation may help the interpretation of the previous result that Notch1 conditional deletion caused no apparent abnormalities in murine spermatogenesis.

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A sensitized genetic screen to identify regulators of Caenorhabditis elegans germline stem cells

Cited by 3 publications

References 30 publications

C. elegans Germline as Three Distinct Tumor Models

C. elegans Germline as Three Distinct Tumor Models

C. elegans Germline as Three Distinct Tumor Models

Analysis of Notch1 signaling in mammalian sperm development

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