美國斯坦福大學醫(yī)學院新近發(fā)現(xiàn)，慢性炎癥可引發(fā)血液干細胞與一種神經(jīng)細胞大量融合,。研究結(jié)果刊登于4月20日的《自然·細胞生物學》電子版,。
研究發(fā)現(xiàn),，患有皮炎的老鼠，其血液干細胞和浦肯雅細胞融合的數(shù)量比普通老鼠高100多倍,。融合后,，血細胞的細胞核表現(xiàn)出原本沉默的神經(jīng)元性狀的基因，這引起干細胞研究人員的極大興趣,。該研究也許能為細胞中介的基因治療開辟新途徑,。
研究者觀察到，大多數(shù)老鼠腦中有不足10個融合細胞,，而有些老鼠腦中的融合細胞高達幾百個,，這些老鼠被發(fā)現(xiàn)患有一種會影響整個免疫系統(tǒng)的先天潰瘍性皮炎。研究者最終確認,，該皮炎與細胞融合之間存在聯(lián)系,。另外還發(fā)現(xiàn)，患有多發(fā)性硬化癥的老鼠,，體內(nèi)異核體的數(shù)量更高達上千,。
血液干細胞也稱造血干細胞，可轉(zhuǎn)化為所有的血液和免疫細胞,。以前也曾發(fā)現(xiàn)造血干細胞的后代可與其他種類的細胞融合,，但十分少見,，被認為不具備生物學重要性。浦肯雅細胞是小腦中一種較大的涉及平衡的神經(jīng)元,。斯坦福大學科學家認為,，它是老鼠和人類的大腦中唯一能與血液干細胞融合的細胞。
之前為了觀察這類融合,，必須先用致命劑量的放射摧毀老鼠的造血系統(tǒng),，再引入改造過的能表現(xiàn)出綠熒光性狀的造血干細胞。之后通過尋找發(fā)綠熒光的神經(jīng)元,，就可以很容易地檢出腦中的異核體,。然而，高劑量放射也會摧毀在大腦和血液間限制細胞流動的天然障礙,。斯坦福的科學家使用一種新的“異體共生”手術,，使兩只老鼠共享循環(huán)系統(tǒng)。一只老鼠被改造為所有細胞都表現(xiàn)綠熒光性狀,，由于共享血液供應,，另一只老鼠在數(shù)周后也有半數(shù)血細胞表現(xiàn)出綠熒光性狀。在手術后20—26周后,，研究者找到了血細胞和浦肯雅細胞融合的證據(jù),。
生物谷推薦原始出處：
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.
