Long-Term Hypoxia Maintains a State of Dedifferentiation and Enhanced Stemness in Fetal Cardiovascular Progenitor Cells.
Long-Term Hypoxia Maintains a State of Dedifferentiation and Enhanced Stemness in Fetal Cardiovascular Progenitor Cells.
复制标题
DOI：
10.3390/ijms22179382
复制
发表时间：
2021-08-29
影响因子：
5.6
通讯作者：
Kearns-Jonker M
中科院分区：
文献类型：
--
作者：
Knox C;Camberos V;Ceja L;Monteon A;Hughes L;Longo L;Kearns-Jonker M
早期哺乳动物胚胎在低氧环境中存活，并发育成功能齐全、健康的有机体，尽管这种缺氧应激。这表明缺氧在胎儿发育中起调节作用，影响细胞的动员、分化、增殖和存活。长期的低氧环境持续整个妊娠期。阐明心血管干细胞在缺氧条件下存活和茁壮成长的机制将有利于细胞治疗，因为干细胞在梗死心脏的缺氧环境中存活有限。目前的研究探讨了长期缺氧对从高海拔饲养的绵羊中分离的胎儿胰岛-1+心血管祖细胞克隆的影响。细胞在体外1%氧环境中培养，并与对照组胰岛-1+心血管祖细胞在21%氧环境中进行比较。RT-PCR、western blotting、流式细胞术和迁移试验从存活、增殖和信号传导方面评估了对长期缺氧的适应。缺氧诱导非典型Wnt、Notch、AKT、HIF-2α和Yap1转录本。缺氧生态位环境调节这些信号通路，维持胎儿心血管祖细胞的去分化和存活。
Early-stage mammalian embryos survive within a low oxygen tension environment and develop into fully functional, healthy organisms despite this hypoxic stress. This suggests that hypoxia plays a regulative role in fetal development that influences cell mobilization, differentiation, proliferation, and survival. The long-term hypoxic environment is sustained throughout gestation. Elucidation of the mechanisms by which cardiovascular stem cells survive and thrive under hypoxic conditions would benefit cell-based therapies where stem cell survival is limited in the hypoxic environment of the infarcted heart. The current study addressed the impact of long-term hypoxia on fetal Islet-1+ cardiovascular progenitor cell clones, which were isolated from sheep housed at high altitude. The cells were then cultured in vitro in 1% oxygen and compared with control Islet-1+ cardiovascular progenitor cells maintained at 21% oxygen. RT-PCR, western blotting, flow cytometry, and migration assays evaluated adaptation to long term hypoxia in terms of survival, proliferation, and signaling. Non-canonical Wnt, Notch, AKT, HIF-2α and Yap1 transcripts were induced by hypoxia. The hypoxic niche environment regulates these signaling pathways to sustain the dedifferentiation and survival of fetal cardiovascular progenitor cells.
登录
查看更多内容
影响因子：
4.8
作者：
Funakoshi-Tago, M;Sonoda, Y;Kasahara, T
通讯作者：
Kasahara, T
影响因子：
4.8
作者：
George, Anju;Panda, Swarupa;Krishnan, Harinivas Harshan
通讯作者：
Krishnan, Harinivas Harshan
影响因子：
11.2
作者：
Graziani, Irene;Eliasz, Sandra;Bocchetta, Maurizio
通讯作者：
Bocchetta, Maurizio
影响因子：
9.9
作者：
Chen, William W.;Schoeberl, Birgit;Jasper, Paul J.;Niepel, Mario;Nielsen, Ulrik B.;Lauffenburger, Douglas A.;Sorger, Peter K.
通讯作者：
Sorger, Peter K.
缺氧预处理促进心脏干细胞存活和体外心源性分化，涉及 HIF-1 α/apelin/APJ 轴的激活
影响因子：
7.5
作者：
Hou J;Wang L;Long H;Wu H;Wu Q;Zhong T;Chen X;Zhou C;Guo T;Wang T
通讯作者：
Wang T