University of Poitiers Signalisation et Transports Ioniques Membranaires, EA7349, Poitiers Cedex 09, France.
CNRS, INSERM, l'institut du thorax, Université de Nantes, 44000, Nantes, France.
Cell Mol Biol Lett. 2020 Nov 5;25(1):50. doi: 10.1186/s11658-020-00242-9.
Human cardiac stem cells expressing the W8B2 marker (W8B2 CSCs) were recently identified and proposed as a new model of multipotent CSCs capable of differentiating into smooth muscle cells, endothelial cells and immature myocytes. Nevertheless, no characterization of ion channel or calcium activity during the differentiation of these stem cells has been reported.
The objectives of this study were thus to analyze (using the TaqMan Low-Density Array technique) the gene profile of W8B2 CSCs pertaining to the regulation of ion channels, transporters and other players involved in the calcium homeostasis of these cells. We also analyzed spontaneous calcium activity (via the GCaMP calcium probe) during the in vitro differentiation of W8B2 CSCs into cardiac myocytes.
Our results show an entirely different electrophysiological genomic profile between W8B2 CSCs before and after differentiation. Some specific nodal genes, such as Tbx3, HCN, ICaT, L, KV, and NCX, are overexpressed after this differentiation. In addition, we reveal spontaneous calcium activity or a calcium clock whose kinetics change during the differentiation process. A pharmacological study carried out on differentiated W8B2 CSCs showed that the NCX exchanger and IP3 stores play a fundamental role in the generation of these calcium oscillations.
Taken together, the present results provide important information on ion channel expression and intrinsic calcium dynamics during the differentiation process of stem cells expressing the W8B2 marker.
最近发现并提出了一种表达 W8B2 标记物的人类心脏干细胞（W8B2 CSCs），作为一种新的多能干细胞模型，能够分化为平滑肌细胞、内皮细胞和未成熟的心肌细胞。然而，目前还没有报道这些干细胞在分化过程中离子通道或钙活性的特征。
因此，本研究的目的是分析 W8B2 CSCs 调节离子通道、转运体和其他参与这些细胞钙稳态的相关基因的表达谱。我们还分析了 W8B2 CSCs 体外分化为心肌细胞过程中的自发性钙活性（通过 GCaMP 钙探针）。
我们的结果显示，W8B2 CSCs 在分化前后的电生理基因组图谱完全不同。一些特定的节点基因，如 Tbx3、HCN、ICaT、L、KV 和 NCX，在分化后过表达。此外，我们揭示了自发钙活性或钙钟，其动力学在分化过程中发生变化。对分化的 W8B2 CSCs 进行的药理学研究表明，NCX 交换器和 IP3 储存库在这些钙振荡的产生中起着重要作用。
综上所述，本研究结果提供了关于表达 W8B2 标记物的干细胞在分化过程中离子通道表达和内在钙动力学的重要信息。
