Polymerase I and transcript release factor transgenic mice show impaired function of hematopoietic stem cells.
Polymerase I and transcript release factor transgenic mice show impaired function of hematopoietic stem cells.
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聚合酶I和转录释放因子转基因小鼠显示造血干细胞功能受损
DOI：
10.18632/aging.103729
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发表时间：
2020-10-21
期刊：
影响因子：
--
通讯作者：
Qin C
中科院分区：
文献类型：
--
作者：
Bai L;Lyu Y;Shi G;Li K;Huang Y;Ma Y;Cong YS;Zhang L;Qin C
干细胞功能的年龄依赖性下降在衰老中起着关键作用，尽管其分子机制尚不清楚。PTRF/Cavin-1是小窝生物发生和功能的重要组成部分，调控细胞增殖、内吞、信号转导和衰老。本研究旨在利用PTRF转基因小鼠分析PTRF在造血干细胞（hsc）衰老中的作用。采用流式细胞术检测免疫细胞和造血干细胞/祖细胞（hsc和HPCs）的频率。结果表明，与野生型（WT）小鼠相比，PTRF转基因小鼠骨髓中HSC区明显扩大，并表现出G1细胞周期阻滞、SA-β-Gal活性升高和活性氧（ROS）水平升高的衰老表型。在体外和体内，ptrf过表达的造血干细胞也表现出明显较低的自我更新和重建造血能力。实时荧光定量PCR检测衰老相关基因的表达水平。PTRF通过ROS-p38-p16和caveolin-1-p53-p21通路诱导hsc衰老。此外，PTRF+cav-1-/-小鼠表现出与WT小鼠相似的hsc功能，表明PTRF部分通过cav-1诱导hsc衰老。因此PTRF部分通过caveolin-1抑制hsc衰老。
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.
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影响因子：
23.9
作者：
Liu Y;Elf SE;Miyata Y;Sashida G;Liu Y;Huang G;Di Giandomenico S;Lee JM;Deblasio A;Menendez S;Antipin J;Reva B;Koff A;Nimer SD
通讯作者：
Nimer SD
Ptrf转基因小鼠表现出肥胖和脂肪肝
DOI：
10.1111/1440-1681.12920
发表时间：
2018-07-01
影响因子：
2.9
作者：
Li, Qian;Bai, Lin;Wang, Miao
通讯作者：
Wang, Miao
影响因子：
4.5
作者：
Rajab A;Straub V;McCann LJ;Seelow D;Varon R;Barresi R;Schulze A;Lucke B;Lützkendorf S;Karbasiyan M;Bachmann S;Spuler S;Schuelke M
通讯作者：
Schuelke M
小凹必需成分 PTRF/Cavin-1 对细胞衰老的调节
影响因子：
44.1
作者：
Bai, Lin;Deng, Xiaoli;Cong, Yu-Sheng
通讯作者：
Cong, Yu-Sheng
影响因子：
64.8
作者：
Janzen, Viktor;Forkert, Randolf;Scadden, David T.
通讯作者：
Scadden, David T.