Aging disrupts spatiotemporal regulation of germline stem cells and niche integrity DOI Creative Commons
Michelle A. Urman, Nimmy S. John,

Tyler Jung

et al.

Biology Open, Journal Year: 2023, Volume and Issue: 13(1)

Published: Dec. 29, 2023

ABSTRACT A major factor driving stem cell decline is niche aging, but its molecular mechanism remains elusive. We use the Caenorhabditis elegans distal tip (DTC), mesenchymal that employs Notch signaling to regulate germline cells (GSCs), as an in vivo aging model and delineate details of DTC/niche process. Here, we demonstrate a drastic decrease C. fecundity, which begins even early adulthood, mainly due age-induced disruption spatial regulation Notch-dependent transcription combined with moderate reduction at both tissue cellular levels. Consequently, Notch-responsive GSC pool shifts from end gonad more proximal region, disrupting distal-to-proximal polarity. find this shift dislocation nucleus, associated changes structure morphology DTC/niche. Our findings reveal critical link between physiological niche, their consequences regulation, functions.

Language: Английский

PUF partner interactions at a conserved interface shape the RNA-binding landscape and cell fate in Caenorhabditis elegans DOI Creative Commons
Brian H. Carrick,

Sarah L. Crittenden,

Fan Chen

et al.

Developmental Cell, Journal Year: 2024, Volume and Issue: 59(5), P. 661 - 675.e7

Published: Jan. 29, 2024

Protein-RNA regulatory networks underpin much of biology. C. elegans FBF-2, a PUF-RNA-binding protein, binds over 1,000 RNAs to govern stem cells and differentiation. FBF-2 interacts with multiple protein partners via key tyrosine, Y479. Here, we investigate the in vivo significance partnerships using Y479A mutant. Occupancy mutant increases or decreases at specific sites across transcriptome, varying RNAs. Germline development also changes fashion: abolishes one function-the sperm-to-oocyte cell fate switch. Y479A's effects on regulation mRNA, gld-1, are critical this change, though other network important. switches from repression activation gld-1 RNA, likely by distinct partnerships. The role RNA-binding governing RNA will extend broadly, as such pervade controls virtually all metazoan tissues species.

Language: Английский

Citations

3
Comprehensive comparative analysis of the effects of temperature on the Notch signaling responsein vivo DOI Creative Commons
Nimmy S. John,

Kin Tang,

Michelle A. Urman

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 19, 2025

Abstract Temperature is a critical factor that modulates cellular metabolism and stem cell regulation. Despite extensive studies, the influence of temperature on regulation via Notch signaling has been limited to studies relying involve indirect readouts activation. This study systematically analyzes effects transcriptional response at chromosomal, cellular, tissue levels. Using complementary direct readouts, we demonstrate activation remains largely unchanged across temperatures, suggesting presence temperature-compensatory mechanisms maintain robust activity however, increased with temperature, indicating elevated temperatures may enhance chromosomal level. These findings provide comprehensive framework for understanding offer new insights into in biology.

Language: Английский

Citations

0
PLAU is associated with cell migration and invasion and is regulated by transcription factor YY1 in cervical cancer DOI Creative Commons
Yanjun Gao,

Xinmei Ma,

Huanxi Lu

et al.

Oncology Reports, Journal Year: 2022, Volume and Issue: 49(2)

Published: Dec. 13, 2022

Cervical cancer, one of the most common malignancies, has a poor survival rate. The identification more biomarkers for cervical cancer diagnosis and therapy is urgently needed. Plasminogen activator urokinase (PLAU) exerts multiple biological effects in various physiological pathological processes; however role PLAU progression not fully understood. In present study, involvement transcriptional regulation were explored. expression was first analyzed, found to be overexpressed. vitro experiments demonstrated that migration invasion HeLa HT3 cells significantly suppressed by knockdown. Additionally, core promoter confirmed, transcription factor YinYang 1 (YY1) regulate mRNA expression. Overall, study elucidated direct association between suggesting YY1/PLAU axis as potential novel therapeutic target cancer.

Language: Английский

Citations

14
LST-1 is a bifunctional regulator that feeds back on Notch-dependent transcription to regulate C. elegans germline stem cells DOI Creative Commons
Ahlan Sabah Ferdous, Tina R. Lynch, Stephany J. Costa Dos Santos

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(39)

Published: Sept. 20, 2023

Notch signaling regulates stem cells across animal phylogeny. C. elegans activates transcription of two genes, lst-1 and sygl-1, that encode potent regulators germline cells. The LST-1 protein in distinct ways: It promotes self-renewal posttranscriptionally also restricts by a poorly understood mechanism. Its promoting activity resides its N-terminal region, while restricting C-terminal region requires the Zn finger. Here, we report limits down-regulating Notch-dependent transcription. We detect nucleus, addition to previously known cytoplasmic localization. lowers nascent transcript levels at both sygl-1 loci but not let-858, Notch-independent locus. key components activation complex, LAG-1 DNA binding intracellular domain (NICD). Genetically, an finger mutant increases strength gain- loss-of-function GLP-1/Notch receptor mutants. Biochemically, co-immunoprecipitates with from nematode extracts, suggesting direct effect. is thus bifunctional regulator coordinates posttranscriptional transcriptional mechanisms single protein. This bifunctionality relies on bipartite architecture bolstered generation isoforms, one specialized for downregulation. A conserved theme worms human coupling PUF-mediated RNA repression together feedback same

Language: Английский

Citations

8
Analysis of the C. elegans Germline Stem Cell Pool DOI

Sarah L. Crittenden,

Hannah S. Seidel, Judith Kimble

et al.

Methods in molecular biology, Journal Year: 2023, Volume and Issue: unknown, P. 1 - 36

Published: Jan. 1, 2023

Language: Английский

Citations

7
Aging disrupts spatiotemporal regulation of germline stem cells and niche integrity DOI Creative Commons
Michelle A. Urman, Nimmy S. John,

Tyler Jung

et al.

Biology Open, Journal Year: 2023, Volume and Issue: 13(1)

Published: Dec. 29, 2023

ABSTRACT A major factor driving stem cell decline is niche aging, but its molecular mechanism remains elusive. We use the Caenorhabditis elegans distal tip (DTC), mesenchymal that employs Notch signaling to regulate germline cells (GSCs), as an in vivo aging model and delineate details of DTC/niche process. Here, we demonstrate a drastic decrease C. fecundity, which begins even early adulthood, mainly due age-induced disruption spatial regulation Notch-dependent transcription combined with moderate reduction at both tissue cellular levels. Consequently, Notch-responsive GSC pool shifts from end gonad more proximal region, disrupting distal-to-proximal polarity. find this shift dislocation nucleus, associated changes structure morphology DTC/niche. Our findings reveal critical link between physiological niche, their consequences regulation, functions.

Language: Английский

Citations

4