Feeder-free generation and characterization of endocardial and cardiac valve cells from human pluripotent stem cells.
Feeder-free generation and characterization of endocardial and cardiac valve cells from human pluripotent stem cells.
复制标题
人多能干细胞内皮细胞和心脏瓣膜细胞的无饲养层产生和表征。
DOI：
10.1016/j.isci.2023.108599
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发表时间：
2024-01-19
期刊：
影响因子：
5.8
通讯作者：
Gelb, Bruce D.
中科院分区：
文献类型：
--
作者：
Liu, Clifford Z.;Prasad, Aditi;Jadhav, Bharati;Liu, Yu;Gu, Mingxia;Sharp, Andrew J.;Gelb, Bruce D.
瓣膜性心脏病是一种严重的健康负担，但瓣膜生物学和治疗学的进展受到缺乏人类瓣膜细胞的阻碍。在这项研究中，我们开发了一种可扩展的无饲养层的方法，将人诱导多能干细胞（iPSC）分化为内皮细胞，其在转录和表型上与血管内皮细胞不同。这些内皮细胞可以被激发进行内皮间质转化（EndMT），之后出现两个不同的群体-一个群体经历EndMT成为瓣膜间质细胞（VIC），而另一个群体加强其内皮身份成为瓣膜内皮细胞（VEC）。然后，我们通过批量RNA-seq转录组分析来表征这些群体，并将我们的维克和VEC群体与从15周龄人类胎儿的正常瓣膜组织产生的伪批量数据进行比较。通过增加这些细胞群的可及性，我们的目标是加速心脏瓣膜生物学和疾病的发现。人iPSCs可以通过BMP 10分化为内皮细胞内皮细胞不同于VEGF衍生的血管内皮细胞内皮细胞经历EndMT形成瓣膜间质细胞一些内皮细胞逃避EndMT成为瓣膜内皮细胞生物科学;发育生物学;心脏病学;干细胞研究
Valvular heart disease presents a significant health burden, yet advancements in valve biology and therapeutics have been hindered by the lack of accessibility to human valve cells. In this study, we have developed a scalable and feeder-free method to differentiate human induced pluripotent stem cells (iPSCs) into endocardial cells, which are transcriptionally and phenotypically distinct from vascular endothelial cells. These endocardial cells can be challenged to undergo endothelial-to-mesenchymal transition (EndMT), after which two distinct populations emerge—one population undergoes EndMT to become valvular interstitial cells (VICs), while the other population reinforces their endothelial identity to become valvular endothelial cells (VECs). We then characterized these populations through bulk RNA-seq transcriptome analyses and compared our VIC and VEC populations to pseudobulk data generated from normal valve tissue of a 15-week-old human fetus. By increasing the accessibility to these cell populations, we aim to accelerate discoveries for cardiac valve biology and disease. Human iPSCs can be differentiated into endocardial cells with BMP10 Endocardial cells are distinct from VEGF-derived vascular endothelial cells Endocardial cells undergo EndMT to form valvular interstitial cells Some endocardial cells escape EndMT to become valvular endothelial cells Biological sciences; Developmental biology; Cardiology; Stem cell research
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DOI：
10.1007/s12265-011-9312-0
发表时间：
2011-12-01
影响因子：
3.4
作者：
Bischoff, Joyce;Aikawa, Elena
通讯作者：
Aikawa, Elena
影响因子：
15.9
作者：
Jain, Rajan;Engleka, Kurt A.;Epstein, Jonathan A.
通讯作者：
Epstein, Jonathan A.
影响因子：
2.4
作者：
Kodigepalli KM;Thatcher K;West T;Howsmon DP;Schoen FJ;Sacks MS;Breuer CK;Lincoln J
通讯作者：
Lincoln J
影响因子：
7.8
作者：
Liebner, S;Cattelino, A;Dejana, E
通讯作者：
Dejana, E
影响因子：
2.6
作者：
Kulkarni, Rishikesh M.;Greenberg, James M.;Akeson, Ann L.
通讯作者：
Akeson, Ann L.