血細胞壽命有限，要求肌體不斷地更新血液,。歐洲分子生物學實驗室（European Molecular Biology Laboratory,，EMBL）研究員Claus Nerlov率領的研究小組和瑞典Lund大學Sten Eirik Jacobsen實驗室合作,，揭示細胞內與血細胞更新有關的信號傳遞途徑（此信號途徑發(fā)生缺陷或者干細胞發(fā)育缺陷經常會導致白血病等疾?。Ｑ芯拷Y果刊登于本周電子版《Nature Immunology》雜志,。
過去幾十年中,，分子生物學家已經鑒別出細胞內控制重大生物學過程的若干種信號傳遞途徑，“Wingless”途徑便是其中之一,。Wingless途徑幾乎存在于所有動物的胚胎發(fā)育過程中,，與組織和器官形成息息相關，而且對于維持干細胞的穩(wěn)定性,、在時機成熟之前抑制干細胞分化有重要作用,。這樣的途徑的開啟和關閉經常是由細胞外的刺激控制的?，F(xiàn)在Nerlov等研究的是：小鼠造血干細胞中Wingless途徑過表達會造成怎樣的后果。
Wingless有助于血細胞分化,，但是對于造血干細胞中這種信號途徑的具體機制還不是很清楚,。研究人員說：“我們修改了Wingless途徑中的β-catenin蛋白，新蛋白能夠“沉浸”傳送狀態(tài)中,，因此細胞中此途徑一直處于開啟狀態(tài),。”
正常情況下，造血干細胞要經歷數(shù)不盡的過渡階段才能完全分化成熟,。分化過程中有幾種血細胞完全消失了,。相同的情況發(fā)生在比造血干細胞還要“分化原始狀態(tài)”的骨髓（bone marrow）。骨髓是重要的造血及免疫器官,。血液的所有細胞成分都來源于造血干細胞，其中髓系細胞（紅細胞系,、粒細胞系,、單核細胞系與巨核細胞-血小板系）是完全在骨髓內分化生成的；淋巴系細胞（T細胞與B細胞）的發(fā)育前期是在骨髓內完成,，但是B細胞和T細胞通過不同的途徑在發(fā)育的早期即已開始分道揚鑣,。暗示這些分化過程可能由Wingless途徑中的某些蛋白控制。β-catenin引人注目,，其在干細胞離開骨髓干細胞庫之前就已經為細胞指明了發(fā)育方向,。
新的研究證實，β-catenin在決定造血干細胞轉化為血細胞與否的決策中扮演主角,；Wingless途徑過表達對已經轉化的細胞不會造成影響,，研究人員推斷β-catenin的作用相對于維持現(xiàn)有細胞活力來說，更像是決定細胞中何種信息通過的指揮官,。
研究人員把造血干細胞比做立在迷宮交叉口左右為難的游戲者,，“我們知道細胞分化、發(fā)育和死亡之間有很強的聯(lián)系,。假如細胞不能在正確的時間選擇正確的發(fā)育路線的話,，很有可能死亡或者畸形生長，急性白血病和其它一些癌癥就是這些錯誤選擇造成的,，因此弄清它們的發(fā)生過程需要精確定位其歧路的最初點,。
英文原文：
A group of molecules controls the numbers and types of blood cell
Scientists have uncovered a group of molecules that controls the numbers and types of blood cell in the body. Defects in this system frequently lead to leukaemia and other diseases. The researchers hope their findings will contribute to our understanding of the intracellular processes that can lead to cancers.
Scientists identified a number of molecular pathways in cells which control major biological processes. They are usually switched on and off by external factors, helping cells respond to their environment. One, the 'Wingless' pathway is found in almost all animals, where it plays a fundamental role in the development of tissues and organs. It also manages stem cells; deciding when they should remain as stem cells and when they should differentiate into other types of cell.
In the current study, researchers from the European Molecular Biology Laboratory (EMBL) and the University of Lund in Sweden investigated what happens when the Wingless pathway is too active in blood stem cells in mice. Their findings are published in the latest edition of Nature Immunology.
'We modified one element of the pathway, a protein called beta-catenin, so that it was stuck in 'transmission mode',' explained Peggy Kirstetter of the EMBL. 'This created cells in which the pathway was always switched on. We've known that Wingless contributes to blood differentiation, but didn't know how the signals were being transmitted within the hematopoietic stem cell.'
When the pathway is working normally, stem cells go through several steps before becoming fully differentiated blood cells. When the researchers stimulated the pathway, several types of blood cell disappeared completely, while others had their development blocked at various stages of differentiation. In mouse bone marrow, some types of stem cell disappeared, while others were too frequent.
The researchers' results show that beta-catenin plays a key role in determining whether blood cells form or not. Furthermore, beta-catenin seems to make cells take decisions about their fate before they leave the stem cell compartment in the bone marrow.
Claus Nerlov of the EMBL explained the implications of his team's findings. 'We know there are strong connections to cells' decisions to divide, to develop, or to die,' he said. 'If cells don't commit themselves to the right developmental path at the right time, they're very likely to die or to begin and inappropriate type of reproduction. Acute leukemias and other forms of cancer cells derive from defects such as this. Understanding the processes by which they form will require pinpointing the forks in the road where things go wrong.'
