血细胞寿命有限，要求肌体不断地更新血液。欧洲分子生物学实验室（European Molecular Biology Laboratory，EMBL）研究员Claus Nerlov率领的研究小组和瑞典Lund大学Sten Eirik Jacobsen实验室合作，揭示细胞内与血细胞更新有关的信号传递途径（此信号途径发生缺陷或者干细胞发育缺陷经常会导致白血病等疾病）。研究结果刊登于本周电子版《Nature Immunology》杂志。
过去几十年中，分子生物学家已经鉴别出细胞内控制重大生物学过程的若干种信号传递途径，“Wingless”途径便是其中之一。Wingless途径几乎存在于所有动物的胚胎发育过程中，与组织和器官形成息息相关，而且对于维持干细胞的稳定性、在时机成熟之前抑制干细胞分化有重要作用。这样的途径的开启和关闭经常是由细胞外的刺激控制的。现在Nerlov等研究的是：小鼠造血干细胞中Wingless途径过表达会造成怎样的后果。
Wingless有助于血细胞分化，但是对于造血干细胞中这种信号途径的具体机制还不是很清楚。研究人员说：“我们修改了Wingless途径中的β-catenin蛋白，新蛋白能够“沉浸”传送状态中，因此细胞中此途径一直处于开启状态。”
正常情况下，造血干细胞要经历数不尽的过渡阶段才能完全分化成熟。分化过程中有几种血细胞完全消失了。相同的情况发生在比造血干细胞还要“分化原始状态”的骨髓（bone marrow）。骨髓是重要的造血及免疫器官。血液的所有细胞成分都来源于造血干细胞，其中髓系细胞（红细胞系、粒细胞系、单核细胞系与巨核细胞-血小板系）是完全在骨髓内分化生成的；淋巴系细胞（T细胞与B细胞）的发育前期是在骨髓内完成，但是B细胞和T细胞通过不同的途径在发育的早期即已开始分道扬镳。暗示这些分化过程可能由Wingless途径中的某些蛋白控制。β-catenin引人注目，其在干细胞离开骨髓干细胞库之前就已经为细胞指明了发育方向。
新的研究证实，β-catenin在决定造血干细胞转化为血细胞与否的决策中扮演主角；Wingless途径过表达对已经转化的细胞不会造成影响，研究人员推断β-catenin的作用相对于维持现有细胞活力来说，更像是决定细胞中何种信息通过的指挥官。
研究人员把造血干细胞比做立在迷宫交叉口左右为难的游戏者，“我们知道细胞分化、发育和死亡之间有很强的联系。假如细胞不能在正确的时间选择正确的发育路线的话，很有可能死亡或者畸形生长，急性白血病和其它一些癌症就是这些错误选择造成的，因此弄清它们的发生过程需要精确定位其歧路的最初点。
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.'
