scholarly journals Aging germline stem cells in C. elegans

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.

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

eLife ◽  
2018 ◽  
Vol 7 ◽  
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.

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

eLife ◽  
2016 ◽  
Vol 5 ◽  
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.

scholarly journals Biology of the Caenorhabditis elegans Germline Stem Cell System

Genetics ◽  
2019 ◽  
Vol 213 (4) ◽  
pp. 1145-1188 ◽  
Author(s):  
E. Jane Albert Hubbard ◽  
Tim Schedl
Keyword(s):  
Stem Cell ◽  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Control Cell ◽  
Cell System ◽  
Germline Stem Cell ◽  
Cell Systems ◽  
Stem Cell Fate ◽  
C Elegans ◽  
Stem Cell System

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.

Analysis of the C. elegans Germline Stem Cell Pool

2016 ◽  
pp. 1-33 ◽  
Author(s):  
Sarah L. Crittenden ◽  
Hannah S. Seidel ◽  
Judith Kimble
Keyword(s):  
Stem Cell ◽  
Germline Stem Cell ◽  
C Elegans ◽  
Cell Pool ◽  
Stem Cell Pool

Elimination of both cancer stem cells and progenitor cells as essential for tumor eradication.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22179-e22179
Author(s):  
Creticus Petrov Marak ◽  
Achuta Kumar Guddati
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Progenitor Cells ◽  
Cell System ◽  
Differentiated Cells ◽  
Differentiating Agents ◽  
Stem Cell System ◽  
Tumor Eradication ◽  
Stem Cell Pool

e22179 Background: Cancer stem cells (CSC) have been identified in several malignancies. Elimination of CSCs requires precise identification of markers and development of mechanisms to target them specifically. It is possible that in spite of elimination of CSCs, the tumor may recur. Dedifferentiation of progenitor cells may help replenish cancer stem cells. Methods: A mathematical model of a cancer stem cell system with four layers has been constructed to reflect the hierarchy of cancer stem cells, progenitor cells and, transit-amplifying cells and pre-differentiated cells. This model is constructed in the lines of the phase space model described by Kirkland. Dedifferentiation parameters were introduced to allow for dedifferentiation when the stem cell pool receded below 40% of its normal size. The effects of stem cell antagonists (SCA) and differentiating agents (DA) were simulated to study the perturbations caused by them on the growth of the tumor. Results: SCAs when used alone result in the establishment of a new equilibrium across different layers within the tumor by de-differentiation. DAs which act only on progenitor cells cause an increase in the number of cells in the subsequent layers and contribute to an increase in the size of the tumor. DAs which act only on the pre-differentiated layer of cells move cells from this layer into a terminally differentiated layer of cells which results in a new but lower equilibrium. DAs which act on the progenitor, transit amplifying and pre-differentiated cells cause the establishment of a new equilibrium which is lower than that of all agents which act on individual layers of cells. A combination of an SCA and a DA which acts on multiple layers eliminates the re-establishment of a new equilibrium and leads to decline in cell populations in all the layers, thus reducing the possibility of recurrence. Conclusions: SCAs when used individually are not effective in eliminating the tumor. DAs which act only on progenitor cells can fuel tumor growth but DAs which act on multiple layers have a profound effect in slowing the growth of the tumor but do not eliminate the tumor. This model implies that a combination of an SCA and a DA which acts on multiple layers may have a better chance at eliminating the tumor.

scholarly journals Loss of foxo rescues stem cell aging in Drosophila germ line

eLife ◽  
2017 ◽  
Vol 6 ◽  
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.

scholarly journals Brief Note: Effect of Erythropoietin on Polycythemic Mouse Spleen in Vitro IV. Response of the Colony-forming Cells to Erythropoietin

Blood ◽  
1968 ◽  
Vol 32 (2) ◽  
pp. 271-277 ◽  
Author(s):  
HIDEAKI MIZOGUCHI ◽  
YASUSADA MIURA ◽  
FUMIMARO TAKAKU ◽  
KIKU NAKAO
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
In Vitro System ◽  
Cell Pool ◽  
Stem Cell Pool

Abstract It is shown that an in vitro system of assaying the size of an erythropoietin-responsive stem cell pool could be applied to the spleens of polycythemic mice after irradiation and bone marrow transplantation. With this method, the presence of erythropoietin-responsive cells in the spleen was first detected on the second day after transplantation. Therefore, it is considered probable that colony-forming cells and erythropoietin-responsive cells are at different stages of maturation or cell cycle. Furthermore, necessity of erythropoietin for further differentiation of transplanted stem cells into erythroblasts is also suggested.

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