典型 Wnt 信号指导在生物打印心脏组织中生成功能性人类 PSC 衍生房室管心肌细胞。

Cell stem cell Pub Date : 2024-03-07 Epub Date: 2024-02-15 DOI:10.1016/j.stem.2024.01.008
Chenxi Ye, Chuanlai Yang, Heqiang Zhang, Rui Gao, Yingnan Liao, Yali Zhang, Lingjun Jie, Yanhui Zhang, Tong Cheng, Yan Wang, Jie Ren
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引用次数: 0

摘要

创建功能性三维生物打印人类心脏仍然具有挑战性,这主要是由于缺乏一些关键的心脏细胞类型,包括房室管(AVC)心肌细胞,而这些细胞对减慢心房和心室之间的电脉冲至关重要。通过利用单细胞RNA测序分析和三维生物打印技术,我们发现,在特定阶段激活典型Wnt信号,可从人类多能干细胞中生成功能性AVC心肌细胞。这些心肌细胞显示出AVC心肌细胞的形态特征并表达其分子标记,包括转录因子TBX2和MSX2。在预制心脏组织中进行生物打印时,这些心肌细胞成功延迟了电脉冲,证明它们有能力在体外发挥AVC心肌细胞的功能。因此,这些发现不仅确定了典型 Wnt 信号是体外 AVC 心肌细胞分化的关键调控因子,更重要的是,它们为功能性人类心脏的生物制造提供了关键的细胞来源。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Canonical Wnt signaling directs the generation of functional human PSC-derived atrioventricular canal cardiomyocytes in bioprinted cardiac tissues.

The creation of a functional 3D bioprinted human heart remains challenging, largely due to the lack of some crucial cardiac cell types, including the atrioventricular canal (AVC) cardiomyocytes, which are essential to slow down the electrical impulse between the atrium and ventricle. By utilizing single-cell RNA sequencing analysis and a 3D bioprinting technology, we discover that stage-specific activation of canonical Wnt signaling creates functional AVC cardiomyocytes derived from human pluripotent stem cells. These cardiomyocytes display morphological characteristics and express molecular markers of AVC cardiomyocytes, including transcription factors TBX2 and MSX2. When bioprinted in prefabricated cardiac tissues, these cardiomyocytes successfully delay the electrical impulse, demonstrating their capability of functioning as the AVC cardiomyocytes in vitro. Thus, these findings not only identify canonical Wnt signaling as a key regulator of the AVC cardiomyocyte differentiation in vitro, but, more importantly, provide a critical cellular source for the biofabrication of a functional human heart.

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