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Pre-stem cell formation by non-platelet RNA-containing particle fusion

机译:通过不含血小板的RNA颗粒融合形成干细胞

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We found a group of non-platelet RNA-containing particles (NPRCP) in human umbilical cord blood. To understand the origin, characterization and differentiation of NPRCP, we examined cord blood-isolated NPRCP in vitro. The NPRCP range in size from < 1 to 5 μm, have a thin bilayer membrane and various morphological features, contain short RNA and microRNA and express octamer-binding transcription factor 4 (OCT4), sex-determining region Y 2 (SOX2) and DEAD box polypeptide 4 (DDX4). On coculture with nucleated cells from umbilical cord blood, NPRCP fuse to small, active, non-nucleated cells called 'particle fusion-derived non-nucleated cells' (PFDNC). The PFDNC are approximately 8 μm in diameter and are characterized by their twisting movement in culture plates. They can easily move into and out of nucleated cells and finally differentiate into mesenchymal-like cells. In addition, the larger non-nucleated cellular structures that are derived from the aggregation and fusion of multiple NPRCP can further differentiate into large stem cells that also release OCT4- and SOX2-positive non-nucleated small cells. Our data provide strong evidence that NPRCP can fuse into PFDNC, which further differentiate into mesenchymal-like cells. Multiple NPRCP also fuse into other types of large stem cells. We believe that stem cells are derived from NPRCP fusion. There is considerable potential for the use of NPRCP in clinical therapy.
机译:我们在人的脐带血中发现了一组非血小板含RNA的颗粒(NPRCP)。为了了解NPRCP的起源,特征和分化,我们在体外检查了脐血分离的NPRCP。 NPRCP的大小范围小于1至5μm,具有薄的双层膜和各种形态特征,包含短RNA和microRNA,并表达八聚体结合转录因子4(OCT4),性别决定区域Y 2(SOX2)和DEAD盒多肽4(DDX4)。与来自脐带血的有核细胞共培养后,NPRCP融合为小的,活跃的无核细胞,称为“粒子融合衍生无核细胞”(PFDNC)。 PFDNC的直径约为8μm,其特征在于它们在培养板上的扭曲运动。它们可以轻松地移入和移出有核细胞,最后分化为间充质样细胞。此外,源自多个NPRCP的聚集和融合的较大的无核细胞结构可以进一步分化为大型干细胞,这些干细胞也释放出OCT4和SOX2阳性的无核小细胞。我们的数据提供了强有力的证据,表明NPRCP可以融合到PFDNC中,进而进一步分化为间充质样细胞。多个NPRCP也融合到其他类型的大型干细胞中。我们认为干细胞源自NPRCP融合。 NPRCP在临床治疗中具有很大的潜力。

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