Germline Stem and Progenitor Cell Aging in C. elegans

Like many animals and humans, reproduction in the nematode C. elegans declines with age. This decline is the cumulative result of age-related changes in several steps of germline function, many of which are highly accessible for experimental investigation in this short-lived model organism. Here we review recent work showing that a very early and major contributing step to reproductive decline is the depletion of the germline stem and progenitor cell pool. Since many cellular and molecular aspects of stem cell biology and aging are conserved across animals, understanding mechanisms of age-related decline of germline stem and progenitor cells in C. elegans has broad implications for aging stem cells, germline stem cells, and reproductive aging.

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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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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.1164496.626682 ◽

2009 ◽

Author(s):

Robert K Herman

Keyword(s):

Stem Cells ◽

Germline Stem Cells ◽

C Elegans

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YAP/Yorkie in the germline modulates the age-related decline of germline stem cells and niche cells

PLoS ONE ◽

10.1371/journal.pone.0213327 ◽

2019 ◽

Vol 14 (4) ◽

pp. e0213327 ◽

Cited By ~ 1

Author(s):

Deepthy Francis ◽

Bhavna Chanana ◽

Beatriz Fernandez ◽

Benjamin Gordon ◽

Tiffany Mak ◽

...

Keyword(s):

Stem Cells ◽

Germline Stem Cells ◽

Age Related

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Mask R-CNN Based C. Elegans Detection with a DIY Microscope

Biosensors ◽

10.3390/bios11080257 ◽

2021 ◽

Vol 11 (8) ◽

pp. 257

Author(s):

Sebastian Fudickar ◽

Eike Jannik Nustede ◽

Eike Dreyer ◽

Julia Bornhorst

Keyword(s):

Cell Biology ◽

High Throughput Screening ◽

Low Cost ◽

Image Acquisition ◽

Rapid Development ◽

Model Organism ◽

Large Data ◽

Data Set ◽

C Elegans ◽

Do It Yourself

Caenorhabditis elegans (C. elegans) is an important model organism for studying molecular genetics, developmental biology, neuroscience, and cell biology. Advantages of the model organism include its rapid development and aging, easy cultivation, and genetic tractability. C. elegans has been proven to be a well-suited model to study toxicity with identified toxic compounds closely matching those observed in mammals. For phenotypic screening, especially the worm number and the locomotion are of central importance. Traditional methods such as human counting or analyzing high-resolution microscope images are time-consuming and rather low throughput. The article explores the feasibility of low-cost, low-resolution do-it-yourself microscopes for image acquisition and automated evaluation by deep learning methods to reduce cost and allow high-throughput screening strategies. An image acquisition system is proposed within these constraints and used to create a large data-set of whole Petri dishes containing C. elegans. By utilizing the object detection framework Mask R-CNN, the nematodes are located, classified, and their contours predicted. The system has a precision of 0.96 and a recall of 0.956, resulting in an F1-Score of 0.958. Considering only correctly located C. elegans with an [email protected] IoU, the system achieved an average precision of 0.902 and a corresponding F1 Score of 0.906.

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C. elegans germline stem cells and their niche

StemBook ◽

10.3824/stembook.1.95.1 ◽

2014 ◽

Cited By ~ 15

Author(s):

Judith Kimble

Keyword(s):

Stem Cells ◽

Germline Stem Cells ◽

C Elegans

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Antioxidant Effects of Caffeic Acid Lead to Protection of Drosophila Intestinal Stem Cell Aging

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.735483 ◽

2021 ◽

Vol 9 ◽

Author(s):

Xiao Sheng ◽

Yuedan Zhu ◽

Juanyu Zhou ◽

La Yan ◽

Gang Du ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Caffeic Acid ◽

Stress Responses ◽

Adult Stem Cells ◽

Cell Function ◽

Cell Aging ◽

Positive Effects ◽

Age Related ◽

Tissue Aging

The dysfunction or exhaustion of adult stem cells during aging is closely linked to tissue aging and age-related diseases. Circumventing this aging-related exhaustion of adult stem cells could significantly alleviate the functional decline of organs. Therefore, identifying small molecular compounds that could prevent the age-related decline of stem cell function is a primary goal in anti-aging research. Caffeic acid (CA), a phenolic compound synthesized in plants, offers substantial health benefits for multiple age-related diseases and aging. However, the effects of CA on adult stem cells remain largely unknown. Using the Drosophila midgut as a model, this study showed that oral administration with CA significantly delayed age-associated Drosophila gut dysplasia caused by the dysregulation of intestinal stem cells (ISCs) upon aging. Moreover, administering CA retarded the decline of intestinal functions in aged Drosophila and prevented hyperproliferation of age-associated ISC by suppressing oxidative stress-associated JNK signaling. On the other hand, CA supplementation significantly ameliorated the gut hyperplasia defect and reduced environmentally induced mortality, revealing the positive effects of CA on tolerance to stress responses. Taken together, our findings report a crucial role of CA in delaying age-related changes in ISCs of Drosophila.

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Loss of foxo rescues stem cell aging in Drosophila germ line

eLife ◽

10.7554/elife.27842 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 8

Author(s):

Filippo Artoni ◽

Rebecca E Kreipke ◽

Ondina Palmeira ◽

Connor Dixon ◽

Zachary Goldberg ◽

...

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Stem Cell ◽

Ionizing Radiation ◽

Cell Injury ◽

Germ Line ◽

Adult Stem Cell ◽

Cell Aging ◽

Germline Stem Cells ◽

Cell Cycle Reentry

Aging stem cells lose the capacity to properly respond to injury and regenerate their residing tissues. Here, we utilized the ability of Drosophila melanogaster germline stem cells (GSCs) to survive exposure to low doses of ionizing radiation (IR) as a model of adult stem cell injury and identified a regeneration defect in aging GSCs: while aging GSCs survive exposure to IR, they fail to reenter the cell cycle and regenerate the germline in a timely manner. Mechanistically, we identify foxo and mTOR homologue, Tor as important regulators of GSC quiescence following exposure to ionizing radiation. foxo is required for entry in quiescence, while Tor is essential for cell cycle reentry. Importantly, we further show that the lack of regeneration in aging germ line stem cells after IR can be rescued by loss of foxo.

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Stem Cells: Muscle Cells Enwrap Escaped Germline Stem Cells in C. elegans

Current Biology ◽

10.1016/j.cub.2019.01.035 ◽

2019 ◽

Vol 29 (5) ◽

pp. R150-R152

Author(s):

Charlotte A. Kelley ◽

Erin J. Cram

Keyword(s):

Stem Cells ◽

Muscle Cells ◽

Germline Stem Cells ◽

C Elegans

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Regulation of the mitosis/meiosis decision in the Caenorhabditis elegans germline

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2003.1333 ◽

2003 ◽

Vol 358 (1436) ◽

pp. 1359-1362 ◽

Cited By ~ 60

Author(s):

Sarah L. Crittenden ◽

Christian R. Eckmann ◽

Liaoteng Wang ◽

David S. Bernstein ◽

Marvin Wickens ◽

...

Keyword(s):

Stem Cells ◽

Caenorhabditis Elegans ◽

Rna Binding ◽

Rna Binding Proteins ◽

Germline Stem Cells ◽

Puf Proteins ◽

C Elegans ◽

Transcriptional Regulatory ◽

Mitotic Proliferation ◽

Multicellular Organisms

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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