美国斯坦福大学医学院新近发现,慢性炎症可引发血液干细胞与一种神经细胞大量融合。研究结果刊登于4月20日的《自然·细胞生物学》电子版。
研究发现,患有皮炎的老鼠,其血液干细胞和浦肯雅细胞融合的数量比普通老鼠高100多倍。融合后,血细胞的细胞核表现出原本沉默的神经元性状的基因,这引起干细胞研究人员的极大兴趣。该研究也许能为细胞中介的基因治疗开辟新途径。
研究者观察到,大多数老鼠脑中有不足10个融合细胞,而有些老鼠脑中的融合细胞高达几百个,这些老鼠被发现患有一种会影响整个免疫系统的先天溃疡性皮炎。研究者最终确认,该皮炎与细胞融合之间存在联系。另外还发现,患有多发性硬化症的老鼠,体内异核体的数量更高达上千。
血液干细胞也称造血干细胞,可转化为所有的血液和免疫细胞。以前也曾发现造血干细胞的后代可与其他种类的细胞融合,但十分少见,被认为不具备生物学重要性。浦肯雅细胞是小脑中一种较大的涉及平衡的神经元。斯坦福大学科学家认为,它是老鼠和人类的大脑中唯一能与血液干细胞融合的细胞。
之前为了观察这类融合,必须先用致命剂量的放射摧毁老鼠的造血系统,再引入改造过的能表现出绿荧光性状的造血干细胞。之后通过寻找发绿荧光的神经元,就可以很容易地检出脑中的异核体。然而,高剂量放射也会摧毁在大脑和血液间限制细胞流动的天然障碍。斯坦福的科学家使用一种新的“异体共生”手术,使两只老鼠共享循环系统。一只老鼠被改造为所有细胞都表现绿荧光性状,由于共享血液供应,另一只老鼠在数周后也有半数血细胞表现出绿荧光性状。在手术后20—26周后,研究者找到了血细胞和浦肯雅细胞融合的证据。
生物谷推荐原始出处:
Nature Cell Biology (20 Apr 2008), doi: 10.1038/ncb1721, Letters
Myeloid and lymphoid contribution to non-haematopoietic lineages through irradiation-induced heterotypic cell fusion
Jens M. Nygren1,2,3, Karina Liuba1,2, Martin Breitbach4, Simon Stott2,5, Lina Thorén1,2, Wilhelm Roell6, Caroline Geisen4, Philipp Sasse4, Deniz Kirik2,5, Anders Björklund2,5, Claus Nerlov2,7, Bernd K. Fleischmann4, Stefan Jovinge1,2,8 & Sten Eirik W. Jacobsen1,2,9
Recent studies have suggested that regeneration of non-haematopoietic cell lineages can occur through heterotypic cell fusion1, 2, 3 with haematopoietic cells of the myeloid lineage2, 3, 4, 5, 6. Here we show that lymphocytes also form heterotypic-fusion hybrids with cardiomyocytes, skeletal muscle, hepatocytes and Purkinje neurons. However, through lineage fate-mapping we demonstrate that such in vivo fusion of lymphoid and myeloid blood cells does not occur to an appreciable extent in steady-state adult tissues or during normal development. Rather, fusion of blood cells with different non-haematopoietic cell types is induced by organ-specific injuries or whole-body irradiation1, 2, 3, 4, 5, 6, 7, 8, 9, 10, which has been used in previous studies to condition recipients of bone marrow transplants. Our findings demonstrate that blood cells of the lymphoid and myeloid lineages contribute to various non-haematopoietic tissues by forming rare fusion hybrids, but almost exclusively in response to injuries or inflammation.