Journal article
Diminished Jak/STAT Signaling Causes Early-Onset Aging Defects in Stem Cell Cytokinesis
Current biology, v 29(2), pp 256-267.e3
21 Jan 2019
PMID: 30612906
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Tissue renewal becomes compromised with age. Although defects in niche and stem cell behavior have been implicated in promoting age-related decline, the causes of early-onset aging defects are unknown. We have identified an early consequence of aging in germline stem cells (GSCs) in the Drosophila testis. Aging disrupts the unique program of GSC cytokinesis, with GSCs failing to abscise from their daughter cells. Abscission failure significantly disrupts both self-renewal and the generation of differentiating germ cells. Extensive live imaging and genetic analyses show that abscission failure is due to inappropriate retention of F-actin at the intercellular bridges between GSC-daughter cells. Furthermore, F-actin is regulated by the Jak/STAT pathway-increasing or decreasing pathway activity can rescue or exacerbate the age-induced abscission defect, respectively. Even subtle decreases to STAT activity are sufficient to precociously age young GSCs and induce abscission failure. Thus, this work has identified the earliest age-related defect in GSCs and has revealed a unique role for an established niche signaling pathway in controlling stem cell cytokinesis and in regulating stem cell behavior with age.
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Details
- Title
- Diminished Jak/STAT Signaling Causes Early-Onset Aging Defects in Stem Cell Cytokinesis
- Creators
- Kari F. Lenhart - Drexel UniversityBenjamin Capozzoli - University of PennsylvaniaGwen S. D. Warrick - Drexel UniversityStephen DiNardo - Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Publication Details
- Current biology, v 29(2), pp 256-267.e3
- Publisher
- Elsevier
- Number of pages
- 15
- Grant note
- R21AG047915 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) R01GM060804 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) College of Arts and Sciences Biology Department
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000456392000020
- Scopus ID
- 2-s2.0-85060031132
- Other Identifier
- 991019168956504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biology
- Cell Biology