Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
Institute of Molecular Systems Biology at the Department of Health Sciences and Technology, Zurich 8092, Switzerland.
Stem Cell Reports. 2018 Jan 9;10(1):87-100. doi: 10.1016/j.stemcr.2017.11.008. Epub 2017 Dec 14.
The identification of cell surface proteins on stem cells or stem cell derivatives is a key strategy for the functional characterization, isolation, and understanding of stem cell population dynamics. Here, using an integrated mass spectrometry- and microarray-based approach, we analyzed the surface proteome and transcriptome of cardiac progenitor cells (CPCs) generated from the stage-specific differentiation of mouse and human pluripotent stem cells. Through bioinformatics analysis, we have identified and characterized FZD4 as a marker for lateral plate mesoderm. Additionally, we utilized FZD4, in conjunction with FLK1 and PDGFRA, to further purify CPCs and increase cardiomyocyte (CM) enrichment in both mouse and human systems. Moreover, we have shown that NORRIN presented to FZD4 further increases CM output via proliferation through the canonical WNT pathway. Taken together, these findings demonstrate a role for FZD4 in mammalian cardiac development.
鉴定干细胞或其衍生细胞表面蛋白是功能特征描述、分离和了解干细胞群体动力学的关键策略。在这里，我们使用一种整合的基于质谱和微阵列的方法，分析了从小鼠和人多能干细胞的阶段特异性分化产生的心脏祖细胞（CPC）的表面蛋白质组和转录组。通过生物信息学分析，我们已经鉴定和表征了 FZD4 作为侧板中胚层的标志物。此外，我们利用 FZD4 与 FLK1 和 PDGFRA 结合，进一步纯化 CPC，并增加小鼠和人类系统中的心肌细胞（CM）富集。此外，我们已经表明，NORRIN 呈现给 FZD4 通过经典 WNT 途径进一步通过增殖增加 CM 的输出。总之，这些发现表明 FZD4 在哺乳动物心脏发育中起作用。
