Analysis of function of microRNAs in Dlk1-Dio3 region in hematopoietic stem cells

造血干细胞(HSCs，CD34-KSL)具有自我更新活性和多潜能。CD34-KSL组分中的CD150+细胞具有长期的、偏重于髓系的再生活性。我们已经鉴定了针对CD150+CD34-KSL组分的microRNAs，并将microRNA转导的CD34-KSL移植到致死性照射的小鼠体内。然而，我们没有检测到扩大自我更新活性的microRNAs。这在一定程度上是由于HSC的异质性，因为已有报道候选microRNAs在巨核细胞中表达。为了评估这一点，我们对所有成熟血细胞都表达荧光蛋白的小鼠骨髓进行了单细胞移植。我们在HSC组分中除了检测到全谱系HSC外，还检测到髓系限制性再填充细胞，这表明一些候选的microRNAs在谱系承诺而不是自我更新中起作用。

Hematopoietic stem cells (HSCs, CD34-KSL) have self-renewal activity and multipotency. CD150+ cells in CD34-KSL fraction have long-term and myeloid-biased repopulating activity. We have identified microRNAs specific to CD150+CD34-KSL fraction and transplanted microRNA-transduced CD34-KSLs into lethally-irradiated mice. However, we could not detect microRNAs that expanded self-renewal activity. This is, in part, due to HSC heterogeneity because candidate microRNAs have been reported to be expressed in megakaryocytes. To assess this, we performed single-cell transplantation of bone marrows from mice in which all mature blood cells express fluorescent protein. We detected myeloid-restricted repopulating cells in addition to full-lineage HSC in HSC fraction, suggesting that some of candidate microRNAs have a role in lineage commitment rather than self-renewal.