本研究是由中国科学院动物研究所生物膜与膜生物工程国家重点实验室与北京307医院青藤转化医学中心肿瘤学实验室共同合作完成,文章的通讯作者是中科院动物所的刘峰研究院。
研究者首先以斑马鱼为研究对象,进行一系列功能学实验,发现miR-142a-3p在造血细胞中特异性表达,推测它可能在造血中起了重要的作用。为进一步的证实以上推论,研究者通过敲除miR-142a-3p基因,进行了一系列loss of function的实验,实验数据表明miR-142a-3p是HSC形成和T细胞分化过程中不可或缺的因子。进一步研究发现,敲除miR-142a-3p基因影响了造血内皮细胞,进而延缓了最早的HSCs细胞在胚胎中出现的时间。
那么irf7下游又调控什么呢?为了使整个故事更加完整,研究者试图探究更多,最终发现irf7与Gcsfr-Nitric Oxide (NO)炎症信号通路可能相关。同时,他们还发现miR-142a-3p在小鼠造血中也发挥了重要的作用。
原文出处:
miR-142-3p regulates the formation and differentiation of hematopoietic stem cells in vertebrates.
Abstract: Previous studies on developmental hematopoiesis have mainly focused on signaling and transcription factors,while the appreciation of epigenetic regulation including that of microRNAs is recent. Here, we show that in zebrafish and mouse, miR-142-3p is specifically expressed in hematopoietic stem cells (HSCs). Knockdown of miR-142a-3p in zebrafish led to a reduced population of HSCs in the aorta-gonad-mesonephros (AGM) region as well as T-cell defects in the thymus. Mechanistically, miR-142a-3p regulates HSC formation and differentiation through the repression of interferon regulatory factor 7 (irf7)-mediated inflammation signaling. Finally, we show that miR-142-3p is also involved in the development of HSCs in mouse AGM, suggesting that it has a highly conserved role in vertebrates. Together, these findings unveil the pivotal roles that miR-142a-3p plays in the formation and differentiation of HSCs by repressing irf7 signaling.
(本文转载:丁香通)