scholarly journals Chemically Diverse Toxicants Converge on Fyn and c-Cbl to Disrupt Precursor Cell Function

PLoS Biology ◽  
2007 ◽  
Vol 5 (2) ◽  
pp. e35 ◽  
Author(s):  
Zaibo Li ◽  
Tiefei Dong ◽  
Chris Pröschel ◽  
Mark Noble
Keyword(s):  
Cell Function ◽  
Precursor Cell

Abstract 013: Role for β-Arrestins in Stem/Precursor Cell Function and Cardiac Regeneration

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Anna M Gumpert ◽  
Mai Chen ◽  
Henriette Brinks ◽  
Jang-Whan Bae ◽  
Karsten Peppel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Death ◽  
Cell Function ◽  
Ischemic Injury ◽  
Precursor Cells ◽  
Cardiac Repair ◽  
Precursor Cell ◽  
Gpcr Desensitization

Chronic heart failure after myocardial injury (MI) is characterized by an extensive loss of myocytes due to considerable cell death. Bone marrow derived stem cells (BMSCs) can transdifferentiate and show potential for regenerating the myocardium after MI. Stem cell mobilization, egress from the bone marrow and recruitment to the site of injury can be regulated by signals through G protein coupled receptors (GPCRs). βArrestins have signalling and scaffolding functions and act as downstream regulators of GPCR desensitization and endocytosis. We explored the potential role for βArrestins in cardiac precursor cell function, concentrating on BMSCs. Using knockout (KO) mice, we investigated the role βArrestin1 (βArr1) and βArrestin2 (βArr2), their modulation of regenerative competence of BMSCs and their contribution to cardiac repair after ischemic injury. in vitro, we observed that BM derived cells devoid of either βArr1 or βArr2 are slower to proliferate, colonize and migrate, compared to wild type (WT) BM cells. We also observed elevated cell death in βArr2 deficient cells following oxidative stress. Additionally, the number of cKit+ stem cells, thought to be potential cardiac precursor cells, was significantly lower in the BM and blood of βArr KO vs WT. Similarly, BM and blood of the chimeras contained fewer and less viable cardiac stem/precursor cells pre and post MI, compared to WT transplanted controls. In our in vivo study, we carried out BM transplants to determine whether the βArrs may be involved in cardiac repair. WT mice were irradiated and received BM transplants from WT, βArr1 KO or βArr2 KO mice. Following BM reconstitution, mice underwent MI and their recovery was monitored. Interestingly, chimeric mice with βArr1 and βArr2 KO BM had significantly inferior outcomes, including significantly decreased post MI survival with βArr2 KO BM and both βArr chimeras had significantly lower cardiac function post MI than mice receiving WT BM. Histology revealed that both chimeras developed larger infarcts and hypertrophy at an faster rate. We conclude that βArrs play a novel role downstream of GPCR desensitization in cardiac progenitor cells in BM and appear to be critically involved in the heart’s response to ischemic injury via cardiac repair and regeneration.

Redox State as a Central Modulator of Precursor Cell Function

2006 ◽  
Vol 991 (1) ◽  
pp. 251-271 ◽  
Author(s):  
MARK NOBLE ◽  
JOEL SMITH ◽  
JENNIFER POWER ◽  
MARGOT MAYER-PRÖSCHEL
Keyword(s):  
Redox State ◽  
Cell Function ◽  
Precursor Cell

scholarly journals Age-related impairment of T cell-induced skeletal muscle precursor cell function

2011 ◽  
Vol 300 (6) ◽  
pp. C1226-C1233 ◽  
Author(s):  
Breanna R. Dumke ◽  
Simon J. Lees
Keyword(s):  
Skeletal Muscle ◽  
T Cells ◽  
T Cell ◽  
Cell Function ◽  
Critical Role ◽  
Interleukin 2 ◽  
Precursor Cell ◽  
Muscle Precursor ◽  
Age Related ◽  
Muscle Precursor Cell

Sarcopenia is the age-associated loss of skeletal muscle mass and strength. Recent evidence suggests that an age-associated loss of muscle precursor cell (MPC) functionality contributes to sarcopenia. The objectives of the present study were to examine the influence of activated T cells on MPCs and determine whether an age-related defect in this signaling occurs. MPCs were collected from the gastrocnemius and plantaris of 3-mo-old (young) and 32-mo-old (old) animals. Splenic T cells were harvested using anti-CD3 Dynabead isolation. T cells were activated for 48 h with costimulation of 100 IU/ml interleukin-2 (IL-2) and 5 μg/ml of anti-CD28. Costimulation increased 5-bromo-2′-deoxyuridine incorporation of T cells from 13.4 ± 4.6% in control to 64.8 ± 6.0% in costimulated cells. Additionally, T cell cytokines increased proliferation on MPCs isolated from young muscle by 24.0 ± 5.7%, whereas there was no effect on MPCs isolated from aged muscle. T cell cytokines were also found to be a chemoattractant. T cells were able to promote migration of MPCs isolated from young muscle; however, MPCs isolated from aged muscle did not respond to the T cell-released chemokines. Conversely, whereas T cell-released cytokines did not affect myogenesis of MPCs isolated from young animals, there was a decrease in MPCs isolated from old animals. These data suggest that T cells may play a critical role in mediating MPC function. Furthermore, aging may alter T cell-induced MPC function. These findings have implications for developing strategies aimed at increasing MPC migration and proliferation leading to an improved regenerative capacity of aged skeletal muscle.

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