Precardiac organoids form two heart fields via Bmp/Wnt signaling.

Precardiac organoids form two heart fields via Bmp/Wnt signaling.
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DOI:
10.1038/s41467-018-05604-8
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发表时间:
2018-08-07
影响因子:
16.6
通讯作者:
Kwon C
Kwon C
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Andersen P;Tampakakis E;Jimenez DV;Kannan S;Miyamoto M;Shin HK;Saberi A;Murphy S;Sulistio E;Chelko SP;Kwon C

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第一心脏区域(FHF)和第二心脏区域(SHF)的发现使我们了解了心脏谱系和结构在发育过程中是如何产生的。然而,如何具体规定这些条款仍不得而知。在这里,我们产生心前球体与多能干细胞(PSC)窝藏GFP/RFP报告的FHF/SHF标志物的控制下,分别。GFP+细胞和RFP+细胞出现在两个不同的区域,并以互补的方式发育。转录组分析显示与胚胎FHF/SHF细胞高度相似。Bmp和Wnt是最差异调节的途径之一,功能获得和丧失研究表明,Bmp分别通过Bmp/Smad途径和Wnt信号传导指定GFP+细胞和RFP+细胞。FHF/SHF细胞可以通过表面蛋白Cxcr 4在没有报告基因的情况下分离。这项研究为理解两个心脏起源的规范提供了新的见解,这可以用于基于PSC的心脏领域/腔室特异性疾病的建模。心脏起源于第一和第二心脏区域(FHF和SHF)的不同祖细胞。在这里,作者从小鼠和人类多能细胞中产生了心前体类器官,并表明FHF和SHF细胞分别响应BMP和Wnt信号传导而形成类似于其体内对应物。
The discovery of the first heart field (FHF) and the second heart field (SHF) led us to understand how cardiac lineages and structures arise during development. However, it remains unknown how they are specified. Here, we generate precardiac spheroids with pluripotent stem cells (PSCs) harboring GFP/RFP reporters under the control of FHF/SHF markers, respectively. GFP+ cells and RFP+ cells appear from two distinct areas and develop in a complementary fashion. Transcriptome analysis shows a high degree of similarities with embryonic FHF/SHF cells. Bmp and Wnt are among the most differentially regulated pathways, and gain- and loss-of-function studies reveal that Bmp specifies GFP+ cells and RFP+ cells via the Bmp/Smad pathway and Wnt signaling, respectively. FHF/SHF cells can be isolated without reporters by the surface protein Cxcr4. This study provides novel insights into understanding the specification of two cardiac origins, which can be leveraged for PSC-based modeling of heart field/chamber-specific disease. The heart arises from distinct progenitor cells of both the first and second heart fields (FHF and SHF). Here, the authors generated precardiac organoids from mouse and human pluripotent cells and show that FHF and SHF cells form similarly to their in vivo counterparts in response to BMP and Wnt signalling, respectively.
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