Research Paper Volume 12, Issue 20 pp 20152—20162
Polymerase I and transcript release factor transgenic mice show impaired function of hematopoietic stem cells
- 1 NHC Key Laboratory of Human Disease Comparative Medicine, The Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China
- 2 Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing 100021, China
- 3 Institute of Aging Research, Hangzhou Normal University School of Medicine, Hangzhou 310036, China
Received: January 6, 2020 Accepted: June 22, 2020 Published: October 21, 2020https://doi.org/10.18632/aging.103729
How to Cite
Copyright: © 2020 Bai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The age-dependent decline in stem cell function plays a critical role in aging, although the molecular mechanisms remain unclear. PTRF/Cavin-1 is an essential component in the biogenesis and function of caveolae, which regulates cell proliferation, endocytosis, signal transduction and senescence. This study aimed to analyze the role of PTRF in hematopoietic stem cells (HSCs) senescence using PTRF transgenic mice. Flow cytometry was used to detect the frequency of immune cells and hematopoietic stem/progenitor cells (HSCs and HPCs). The results showed than the HSC compartment was significantly expanded in the bone marrow of PTRF transgenic mice compared to age-matched wild-type (WT) mice, and exhibited the senescent phenotype characterized by G1 cell cycle arrest, increased SA-β-Gal activity and high levels of reactive oxygen species (ROS). The PTRF-overexpressing HSCs also showed significantly lower self-renewal and ability to reconstitute hematopoiesis in vitro and in vivo. Real-time PCR was performed to analyze the expression levels of senescence-related genes. PTRF induced HSCs senescence via the ROS-p38-p16 and caveolin-1-p53-p21 pathways. Furthermore, the PTRF+cav-1-/- mice showed similar HSCs function as WT mice, indicating that PTRF induces senescence in HSCs partly through caveolin-1. Thus PTRF impaired HSCs aging partly via caveolin-1.
PTRF: polymerase I and transcript release factor; HSC: hematopoietic stem cells; SA-β-gal: e-association β-galactosidase; ROS: reactive oxygen species; BM: bone marrow; WT: wild type.