Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Lawrence D. Longo MD Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Int J Mol Sci. 2021 Aug 29;22(17):9382. doi: 10.3390/ijms22179382.
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 , , , - and transcripts were induced by hypoxia. The hypoxic niche environment regulates these signaling pathways to sustain the dedifferentiation and survival of fetal cardiovascular progenitor cells.
早期哺乳动物胚胎在低氧张力环境中存活，并发育成完全功能的健康生物体，尽管存在这种低氧应激。这表明，缺氧在胎儿发育中发挥调节作用，影响细胞动员、分化、增殖和存活。长期的低氧环境在整个妊娠期持续存在。阐明心血管干细胞在低氧条件下存活和茁壮成长的机制将有益于基于细胞的治疗，其中在梗死心脏的低氧环境中，干细胞的存活受到限制。本研究探讨了长期低氧对从高海拔地区饲养的绵羊中分离出的胎儿 Islet-1+心血管祖细胞克隆的影响。然后，将这些细胞在 1%氧气中进行体外培养，并与在 21%氧气中维持的对照 Islet-1+心血管祖细胞进行比较。RT-PCR、Western blot、流式细胞术和迁移实验评估了细胞在长期低氧条件下的存活、增殖和信号转导方面的适应能力。非典型的 、 、 、 和 转录本被低氧诱导。低氧生态位环境调节这些信号通路，以维持胎儿心血管祖细胞的去分化和存活。
