Derivation of proliferative islet1-positive cells during metamorphosis and wound response in Xenopus

Derivation of proliferative islet1-positive cells during metamorphosis and wound response in Xenopus
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DOI:
10.1007/s00418-020-01929-y
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发表时间:
2020-10
影响因子:
2.3
通讯作者:
Saki Umezawa;M. Miyakawa;Takashi Yamaura;H. Kubo;T. Kinoshita
Saki Umezawa;M. Miyakawa;Takashi Yamaura;H. Kubo;T. Kinoshita
中科院分区:
生物学3区
文献类型:
--
作者:
Saki Umezawa;M. Miyakawa;Takashi Yamaura;H. Kubo;T. Kinoshita

文献摘要

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在哺乳动物心脏中,心肌细胞在出生前损伤后保留短暂的增殖和再生能力,而出生后立即失去增殖能力。还已知包括islet1阳性细胞的心脏祖细胞对哺乳动物的心脏修复和再生没有贡献。相比之下,斑马鱼、两栖动物和爬行动物的心脏在整个生命周期中都保持着再生能力。在这里,我们分析了心脏发育和心室切除后使用Xenopus laevis,特别是集中在胰岛1的心脏细胞的增殖能力。免疫组化结果显示,胰岛1阳性细胞广泛分布于脑室,并在变态后仍保持较高的分裂能力。有趣的是,islet1阳性细胞被保存,甚至在1年后变态,其中一些显示原肌球蛋白表达。为了评估胰岛1阳性细胞作为细胞资源的可能性,使用变态后3个月的成人心脏分析胰岛1对心脏切除的反应。在截肢后1天内检测到根尖区fislet1基因的瞬时激活。组织学分析显示,islet1阳性细胞出现在切除平面附近的截肢后1天(dpa)和增加在3 dpa的原肌球蛋白阳性和原肌球蛋白阴性区域。生物素葡聚糖胺(BDA)血管标记分析表明,在原肌球蛋白阴性区域的胰岛1阳性细胞与心脏血管密切相关。此外,分裂能力在该时间点达到峰值。切除区域愈合与原肌球蛋白阳性的心肌细胞,直到3个月后截肢。这些结果表明,胰岛1阳性细胞的作用作为血管化和心脏发生的细胞资源在非洲爪蟾。
In mammalian hearts, cardiomyocytes retain a transient capacity to proliferate and regenerate following injury before birth, whereas they lose proliferative capacity immediately after birth. It has also been known that cardiac progenitor cells including islet1-positive cells do not contribute to the cardiac repair and regeneration in mammals. In contrast, hearts of zebrafish, amphibians and reptiles maintain a regenerative ability throughout life. Here, we analyzed proliferative capacity of cardiac cells during cardiac development and post-ventricular resection usingXenopus laevis, especially focusing on islet1. Immunohistochemical examination showed that islet1-positive cells were present in a wide range of the ventricle and maintained high dividing ability after metamorphosis. Interestingly, the islet1-positive cells were preserved even at 1 year after metamorphosis, some of which showed tropomyosin expression. To assess the possibility of islet1-positive cells as a cellular resource, islet1 response to cardiac resection was analyzed, using adult hearts of 3 months after metamorphosis. Transient gene activation ofislet1in apical region was detected within 1 day after amputation. Histological analyses revealed that islet1-positive cells appeared in the vicinity of resection plane at 1 day post-amputation (dpa) and increased at 3 dpa in both tropomyosin-positive and tropomyosin-negative regions. Vascular labeling analysis by biotinylated dextran amine (BDA) indicated that the islet1-positive cells in a tropomyosin-negative region were closely associated with cardiac vessels. Moreover, dividing ability at this time point was peaked. The resected region was healed with tropomyosin-positive cardiomyocytes until 3 months post-amputation. These results suggest a role of islet1-positive cells as a cellular resource for vascularization and cardiogenesis inXenopus laevis.