Analysis of the C. elegans Germline Stem Cell Pool

Abstract Failure to maintain stem cells with age is associated with conditions such as tissue degeneration and increased susceptibility to tissue damage. We use the C. elegans germline stem cell system as a model to study stem cell aging. This system combines a well-established model for aging with an accessible stem cell system, providing a unique opportunity to understand how aging influences stem cell dynamics. The germline stem/progenitor pool in in C. elegans becomes depleted over time. At the cellular level, aging influences both the size of the stem cell pool and the proliferation rate of stem cells. The flux of differentiated cells also affects how aging impacts the pool. This depletion is partially alleviated in mutants with reduced insulin/IGF-like signaling via inhibition of the transcription factor DAF-16/FOXO. In this role, DAF-16 does not act in the germ line, and its anatomical requirements are different from its previously described roles in larval germline proliferation, dauer control, and lifespan regulation. We found that DAF-16/FOXO is required in certain somatic cells in the proximal part of the reproductive system to regulate the stem cell pool. We also find that the degree to which various age-defying perturbations affect lifespan does not correlate with their effect on germline stem cell maintenance. We are investigating additional aspects of aging germline stem cells using this system.

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Author response: C. elegans GLP-1/Notch activates transcription in a probability gradient across the germline stem cell pool

10.7554/elife.18370.019 ◽

2016 ◽

Author(s):

ChangHwan Lee ◽

Erika B Sorensen ◽

Tina R Lynch ◽

Judith Kimble

Keyword(s):

Stem Cell ◽

Author Response ◽

Germline Stem Cell ◽

C Elegans ◽

Cell Pool ◽

Stem Cell Pool

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Decision letter: C. elegans GLP-1/Notch activates transcription in a probability gradient across the germline stem cell pool

10.7554/elife.18370.018 ◽

2016 ◽

Keyword(s):

Stem Cell ◽

Germline Stem Cell ◽

C Elegans ◽

Cell Pool ◽

Stem Cell Pool

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Faculty Opinions recommendation of JNK signaling triggers spermatogonial dedifferentiation during chronic stress to maintain the germline stem cell pool in the Drosophila testis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733604418.793550197 ◽

2018 ◽

Author(s):

Todd Nystul

Keyword(s):

Stem Cell ◽

Chronic Stress ◽

Germline Stem Cell ◽

Jnk Signaling ◽

Cell Pool ◽

Drosophila Testis ◽

Stem Cell Pool

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JNK signaling triggers spermatogonial dedifferentiation during chronic stress to maintain the germline stem cell pool in the Drosophila testis

eLife ◽

10.7554/elife.36095 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 11

Author(s):

Salvador C Herrera ◽

Erika A Bach

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Chronic Stress ◽

Germline Stem Cell ◽

Germline Stem Cells ◽

Jnk Signaling ◽

Cell Pool ◽

Drosophila Testis ◽

Bag Of Marbles ◽

Stem Cell Pool

Exhaustion of stem cells is a hallmark of aging. In the Drosophila testis, dedifferentiated germline stem cells (GSCs) derived from spermatogonia increase during lifespan, leading to the model that dedifferentiation counteracts the decline of GSCs in aged males. To test this, we blocked dedifferentiation by mis-expressing the differentiation factor bag of marbles (bam) in spermatogonia while lineage-labeling these cells. Strikingly, blocking bam-lineage dedifferentiation under normal conditions in virgin males has no impact on the GSC pool. However, in mated males or challenging conditions, inhibiting bam-lineage dedifferentiation markedly reduces the number of GSCs and their ability to proliferate and differentiate. We find that bam-lineage derived GSCs have significantly higher proliferation rates than sibling GSCs in the same testis. We determined that Jun N-terminal kinase (JNK) activity is autonomously required for bam-lineage dedifferentiation. Overall, we show that dedifferentiation provides a mechanism to maintain the germline and ensure fertility under chronically stressful conditions.

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Non-Smad-Dependent BMP signaling Determines the size of Germline Stem Cell Pool via the Soma

Mechanisms of Development ◽

10.1016/j.mod.2017.04.504 ◽

2017 ◽

Vol 145 ◽

pp. S174

Author(s):

Chen-Yuan Tseng ◽

Yu-Han Su ◽

Hwei-Jan Hsu

Keyword(s):

Stem Cell ◽

Bmp Signaling ◽

Germline Stem Cell ◽

Cell Pool ◽

Stem Cell Pool

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C. elegans GLP-1/Notch activates transcription in a probability gradient across the germline stem cell pool

eLife ◽

10.7554/elife.18370 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 34

Author(s):

ChangHwan Lee ◽

Erika B Sorensen ◽

Tina R Lynch ◽

Judith Kimble

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Transcriptional Response ◽

Germline Stem Cells ◽

C Elegans ◽

Cell Pool ◽

Transcription Sites ◽

Active Transcription ◽

Nascent Transcripts ◽

Stem Cell Pool

C. elegans Notch signaling maintains a pool of germline stem cells within their single-celled mesenchymal niche. Here we investigate the Notch transcriptional response in germline stem cells using single-molecule fluorescence in situ hybridization coupled with automated, high-throughput quantitation. This approach allows us to distinguish Notch-dependent nascent transcripts in the nucleus from mature mRNAs in the cytoplasm. We find that Notch-dependent active transcription sites occur in a probabilistic fashion and, unexpectedly, do so in a steep gradient across the stem cell pool. Yet these graded nuclear sites create a nearly uniform field of mRNAs that extends beyond the region of transcriptional activation. Therefore, active transcription sites provide a precise view of where the Notch-dependent transcriptional complex is productively engaged. Our findings offer a new window into the Notch transcriptional response and demonstrate the importance of assaying nascent transcripts at active transcription sites as a readout for canonical signaling.

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