Faculty Opinions recommendation of Starvation protects germline stem cells and extends reproductive longevity in C. elegans.

During the development of multicellular organisms, the processes of growth and differentiation are kept in balance to generate and maintain tissues and organs of the correct size, shape and cellular composition. We have investigated the molecular controls of growth and differentiation in the Caenorhabditis elegans germline. A single somatic cell, called the distal tip cell, promotes mitotic proliferation in the adjacent germline by GLP–1/Notch signalling. Within the germline, the decisions between mitosis and meiosis and between spermatogenesis and oogenesis are controlled by a group of conserved RNA regulators. FBF, a member of the PUF (for Pumilio and FBF) family of RNA–binding proteins, promotes mitosis by repressing gld–1 mRNA activity; the GLD–1, GLD–2, GLD–3 and NOS–3 proteins promote entry into meiosis by regulating mRNAs that remain unknown. The regulatory balance between opposing FBF and GLD activities is crucial for controlling the extent of germline proliferation. PUF proteins regulate germline stem cells in both Drosophila and C. elegans and are localized to germline stem cells of the mammalian testis. Therefore, this post–transcriptional regulatory switch may be an ancient mechanism for controlling maintenance of stem cells versus differentiation.

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Systemic regulation of mitochondria by germline proteostasis prevents protein aggregation in the soma of C. elegans

Science Advances ◽

10.1126/sciadv.abg3012 ◽

2021 ◽

Vol 7 (26) ◽

pp. eabg3012

Author(s):

Giuseppe Calculli ◽

Hyun Ju Lee ◽

Koning Shen ◽

Uyen Pham ◽

Marija Herholz ◽

...

Keyword(s):

Stem Cells ◽

Protein Aggregation ◽

Germ Line ◽

Wnt Signaling Pathway ◽

Germline Stem Cells ◽

C Elegans ◽

Unfolded Protein ◽

Somatic Tissues ◽

Intracellular Changes ◽

The Unfolded Protein Response

Protein aggregation causes intracellular changes in neurons, which elicit signals to modulate proteostasis in the periphery. Beyond the nervous system, a fundamental question is whether other organs also communicate their proteostasis status to distal tissues. Here, we examine whether proteostasis of the germ line influences somatic tissues. To this end, we induce aggregation of germline-specific PGL-1 protein in germline stem cells of Caenorhabditis elegans. Besides altering the intracellular mitochondrial network of germline cells, PGL-1 aggregation also reduces the mitochondrial content of somatic tissues through long-range Wnt signaling pathway. This process induces the unfolded protein response of the mitochondria in the soma, promoting somatic mitochondrial fragmentation and aggregation of proteins linked with neurodegenerative diseases such as Huntington’s and amyotrophic lateral sclerosis. Thus, the proteostasis status of germline stem cells coordinates mitochondrial networks and protein aggregation through the organism.

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C. elegans germ cells divide and differentiate along a folded epithelium

10.1101/322487 ◽

2018 ◽

Author(s):

Hannah S. Seidel ◽

Tilmira A. Smith ◽

Jessica K. Evans ◽

Jarred Q. Stamper ◽

Thomas G. Mast ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Germ Cells ◽

Cell Model ◽

Three Dimensional ◽

3D Models ◽

Germline Stem Cells ◽

C Elegans ◽

Stem Cell Regulation ◽

Stem Cell Model

AbstractKnowing how stem cells and their progeny are positioned within their tissues is essential for understanding their regulation. One paradigm for stem cell regulation is the C. elegans germline, which is maintained by a pool of germline stem cells in the distal gonad, in a region known as the ‘progenitor zone’. The C. elegans germline is widely used as a stem cell model, but the cellular architecture of the progenitor zone has been unclear. Here we characterize this architecture by creating virtual 3D models of the progenitor zone in both sexes. We show that the progenitor zone in adult hermaphrodites is essentially a folded epithelium. The progenitor zone in males is not folded. Analysis of germ cell division shows that daughter cells are born side-by-side along the surface of the epithelium. Analysis of a key regulator driving differentiation, GLD-1, shows that germ cells in hermaphrodites differentiate along the path of the folded epithelium, with previously described “steps” in GLD-1 expression corresponding to germline folds. Our study provides a three-dimensional view of how C. elegans germ cells progress from stem cell to overt differentiation, with critical implications for regulators driving this transition.

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Faculty Opinions recommendation of Starvation protects germline stem cells and extends reproductive longevity in C. elegans.

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

10.3410/f.1164496.748062 ◽

2009 ◽

Author(s):

Nektarios Tavernarakis

Keyword(s):

Stem Cells ◽

Germline Stem Cells ◽

C Elegans

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The C. elegans adult male germline: Stem cells and sexual dimorphism

Developmental Biology ◽

10.1016/j.ydbio.2010.07.022 ◽

2010 ◽

Vol 346 (2) ◽

pp. 204-214 ◽

Cited By ~ 37

Author(s):

Dyan E. Morgan ◽

Sarah L. Crittenden ◽

Judith Kimble

Keyword(s):

Stem Cells ◽

Sexual Dimorphism ◽

Adult Male ◽

Germline Stem Cells ◽

C Elegans ◽

Male Germline ◽

Male Germline Stem Cells

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Aging germline stem cells in C. elegans

Innovation in Aging ◽

10.1093/geroni/igaa057.2644 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 740-740

Author(s):

E Jane Hubbard

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell System ◽

Cell Aging ◽

Germline Stem Cell ◽

Germline Stem Cells ◽

C Elegans ◽

Cell Pool ◽

Stem Cell System ◽

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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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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Starvation Protects Germline Stem Cells and Extends Reproductive Longevity in C. elegans

Science ◽

10.1126/science.1178343 ◽

2009 ◽

Vol 326 (5955) ◽

pp. 954-958 ◽

Cited By ~ 168

Author(s):

G. Angelo ◽

M. R. Van Gilst

Keyword(s):

Stem Cells ◽

Germline Stem Cells ◽

C Elegans

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