Stem and progenitor cells of the postnatal CNS

神经生物学最近的一大惊喜是，人们意识到，无论是啮齿动物还是人类，成年大脑中都有干细胞口袋，它们在一生中不断产生新的神经元。大多数？成人出生的？神经元分布在嗅球(一种识别和记忆气味所需的大脑结构)和海马体(一种神秘的结构，涉及对地点和事件的记忆)。对于新神经元的确切作用，我们仍然一无所知。然而，人们普遍感到兴奋的是，因为干细胞在正常条件下可以生成某些类型的神经元，它们可能会有更大的潜力生成神经元，以取代那些因损伤或帕金森？S或阿尔茨海默氏症？S等神经退行性疾病而失去的神经元。这是一个具有挑战性的想法，因为据我们所知，干细胞通常不会产生在这些疾病中被摧毁的那种神经元。问题是，如果我们能学会如何调整，它们有可能制造出我们想要的神经元吗？他们?我们和其他人最近发现，在健康的大脑中，不仅有一种干细胞，还有几种，可能是很多种，具有略有不同的特性，专门在嗅球中制造不同类型的神经元。这是令人鼓舞的，因为这意味着可能还有更多类型的干细胞我们还不知道，也许有些具有我们正在寻找的特性。另一方面，它使情况变得复杂，因为我们现在有更多的单元格要排序。在我们这里描述的工作方案中，我们首先了解不同干细胞亚型在面临不同形式的损害时可能会出现的不同行为，例如缺血(中风期间发生的血液供应中断)或脱髓鞘(神经纤维周围绝缘层的丧失，如多发性硬化症)或运动神经元病的遗传形式(脊髓运动神经元死亡，导致瘫痪)。我们将通过对小鼠进行基因操作，用荧光标签标记一种或另一种干细胞亚型，这样我们就可以在完整的大脑中分别跟踪它们的行为。荧光标签还允许我们在培养皿中分离纯化和研究它们。

One of the big surprises in neurobiology recently has been the realization that there are pockets of stem cells in the adult brain that continuously generate new neurons throughout life, both in rodents and humans. The majority of ?adult-born? neurons populate the olfactory bulb (a brain structure required for recognition and memory of odors) and the hippocampus (an enigmatic structure involved in laying down memories of places and events). We are still in the dark about the precise role of the new neurons. Nevertheless, there is widespread excitement that, because stem cells can generate some types of neurons under normal conditions, they might have a wider potential to generate neurons to replace those that are lost through injury or neurodegenerative diseases like Parkinson?s or Alzheimer?s. This is a challenging idea because, as far as we know, the stem cells do not normally make the kinds of neurons that are destroyed in these diseases. The question is, do they have the potential to make the neurons we want, if only we could learn how to ?tweak? them? We and others recently discovered that there is not just one kind of stem cell in the healthy brain but several, possibly many, that have slightly different properties and that specialize in making different kinds of neurons in the olfactory bulb. This is encouraging because it implies that there might be yet more types of stem cells that we don?t know about yet, perhaps some with the properties we are looking for. On the other hand, it complicates the picture because we now have more cells to sort through. In the programme of work we describe here we make a start towards understanding the different behaviours we might expect from different stem cell subtypes when they are confronted with different forms of damage such as ischemia (interruption of blood supply such as occurs during stroke) or demyelination (loss of the insulating layer around nerve fibres, such as happens in multiple sclerosis) or in a genetic form of motor neuron disease (in which spinal motor neurons die, leading to paralysis. We will do this by genetically manipulating mice to mark one stem cell subtype or the other with a fluorescent label, so that we can follow their behaviour separately in the intact brain. The fluorescent label also allows us to purify and study them separately in a culture dish.