Bmi1 (+) cardiac progenitor cells contribute to myocardial repair following acute injury.
Bmi1 (+) cardiac progenitor cells contribute to myocardial repair following acute injury.
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BMI1（+）心脏祖细胞在急性损伤后有助于心肌修复。
DOI：
10.1186/s13287-016-0355-7
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发表时间：
2016-07-30
影响因子：
7.5
通讯作者：
Bernad A
中科院分区：
文献类型：
--
作者：
Valiente-Alandi I;Albo-Castellanos C;Herrero D;Sanchez I;Bernad A
在严重心脏损伤后，成年哺乳动物的心脏无法替换丢失的细胞，这损害了器官功能。虽然心脏是人体再生能力最低的器官之一，但近几十年来积累的证据表明，心脏在损伤后具有一定程度的再生能力。我们评估了心肌Bmi1+祖细胞（Bmi1- cpc）在急性心肌梗死（AMI）后的作用。Bmi1Cre / +;采用Rosa26YFP/+ (Bmi1-YFP)小鼠进行谱系追踪策略。经他莫昔芬（TM）诱导后，Bmi1+细胞在Rosa26调控序列的控制下表达黄色荧光蛋白（YFP）。心肌梗死后追踪YFP+细胞。此外，在未挑战的心脏和心肌梗死后，对分离的YFP+细胞进行了全转录组分析。对未挑战心脏的Bmi1-CPC进行深度测序分析表明，该人群表达高水平的多能性标记。相反，AMI后Bmi1-CPC的转录组评估显示，与细胞增殖、运动和细胞周期相关的基因具有丰富的代表性。心肌梗死后的谱系追踪研究表明，bmi1表达细胞的后代有助于新生心肌细胞（CM）（13.8±5%的新YFP+ CM，而在年龄配对的非梗死心脏中为4.7±0.9%）。然而，对tm诱导的第1天Bmi1-YFP幼崽的根尖切除表明，bmi1来源的细胞对新生CM的贡献非常小。心脏Bmi1祖细胞对心脏损伤有反应，有助于成年小鼠心脏新生CM的产生。本文的在线版本（doi:10.1186/s13287-016-0355-7）包含补充材料，可供授权用户使用。
The inability of the adult mammalian heart to replace cells lost after severe cardiac injury compromises organ function. Although the heart is one of the least regenerative organs in the body, evidence accumulated in recent decades indicates a certain degree of renewal after injury. We have evaluated the role of cardiac Bmi1+ progenitor cells (Bmi1-CPC) following acute myocardial infarction (AMI). Bmi1Cre/+;Rosa26YFP/+ (Bmi1-YFP) mice were used for lineage tracing strategy. After tamoxifen (TM) induction, yellow fluorescent protein (YFP) is expressed under the control of Rosa26 regulatory sequences in Bmi1+ cells. YFP+ cells were tracked following myocardial infarction. Additionally, whole transcriptome analysis of isolated YFP+ cells was performed in unchallenged hearts and after myocardial infarction. Deep-sequencing analysis of Bmi1-CPC from unchallenged hearts suggests that this population expresses high levels of pluripotency markers. Conversely, transcriptome evaluation of Bmi1-CPC following AMI shows a rich representation of genes related to cell proliferation, movement, and cell cycle. Lineage-tracing studies after cardiac infarction show that the progeny of Bmi1-expressing cells contribute to de novo cardiomyocytes (CM) (13.8 ± 5 % new YFP+ CM compared to 4.7 ± 0.9 % in age-paired non-infarcted hearts). However, apical resection of TM-induced day 1 Bmi1-YFP pups indicated a very minor contribution of Bmi1-derived cells to de novo CM. Cardiac Bmi1 progenitor cells respond to cardiac injury, contributing to the generation of de novo CM in the adult mouse heart. The online version of this article (doi:10.1186/s13287-016-0355-7) contains supplementary material, which is available to authorized users.