不同种类转录因子定向诱导心室肌与心房肌的转分化研究

Directed reprogramming of fibroblasts into functional cardiomyocytes by defined factors is a hot research point in treating myocardial infarction or other diseases, which has promising clinical application potentials and medical research significance for heart disease. However, there are two urgent problems about the cell transdifferentiation for myocardial infarction treatment. One is how to promote the efficiency of transdifferentiation to obtain enough functional cardiac myocyte. The other is how to achieve relative homogeneous ventricle myocytes for experimental or clinical application. Our previous study has set up an efficient system of direct differentiation of cardiac ventricle and atrial myocytes from the monolayer human embryonic stem cells. In this study, we analysis our achieved ventricle and atrial myocyte array data and compare the expression of all the transcriptional factors which are different between the two cell line. Based on this, we are trying to explore the reprogramming of fibroblasts into functional cardiomycytes in animal models, and identify novel transcriptional factors for reprogramming, and especially developed a protocol for directly obtain cardiac myocytes from fibroblast cells with high efficient either. In summary, our proposal is aimed to provide a new avenue for the treatment of myocardial infarction diseases.

利用几种转录因子诱导成纤维细胞到心肌细胞的转分化并同时用于治疗心肌梗死等疾病是当前研究的热点。这一方法的报导引起了巨大的反响，它与细胞移植等传统方法相比具有更强的临床应用潜能。然而转分化对心肌梗死的治疗依然存在着两个亟待解决的问题，一是如何提高转分化的效率;二是如何得到相对单一的心室肌细胞。 我们实验室一直从事人胚胎干细胞定向分化成心房肌细胞和心室肌细胞的研究，且得到了相对单一的细胞类型。在此基础上，我们拟将得到的心室肌及心房肌细胞进行测序，分析得到它们之间相同的和不同的转录因子，并用于进一步的转分化研究，以期提高转分化的效率并得到相对单一的心肌细胞，对临床心肌梗死疾病的治疗打下基础。

利用转录因子诱导成纤维细胞到心肌细胞的转分化并同时用于治疗心肌梗死等疾病是当前研究的热点。转分化对心肌梗死的治疗依然存在着两个亟待解决的问题，一是如何提高转分化的效率;二是如何得到相对单一的心室肌细胞。我们通过调控视黄酸信号通路以及BMP4信号通路，定向分化为心房肌和心室肌细胞。在此基础上，我们将得到的心室肌及心房肌细胞进行测序，分析得到它们之间相同的和不同的转录因子，并用于进一步的转分化研究，以期提高转分化的效率并得到相对单一的心肌细胞。另外，我们通过同时调控视黄酸和Wnt信号通路，得到高纯度的Tbx18+和Wt1+的心外膜细胞，并且这些细胞能分化为血管平滑肌细胞和心脏成纤维细胞。这些研究为临床上心肌梗死疾病的治疗打下基础。