Stem and progenitor cells of the postnatal CNS

最近神经生物学的一个大惊喜是，在啮齿动物和人类的成年大脑中，有一些干细胞在一生中不断产生新的神经元。大多数人是成年出生的？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（一种涉及放置地点和事件记忆的神秘结构）。我们仍然不清楚新神经元的确切作用。然而，令人普遍兴奋的是，由于干细胞在正常条件下可以产生某些类型的神经元，它们可能有更大的潜力来产生神经元，以取代那些因损伤或神经退行性疾病（如帕金森病）而丢失的神经元。还是老年痴呆症？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破坏的那种神经元。问题是，它们是否有潜力制造出我们想要的神经元，只要我们能学会如何调整？他们吗?我们和其他人最近发现，在健康的大脑中，不是只有一种干细胞，而是有几种，可能是许多种，它们的性质略有不同，专门用于在嗅球中制造不同种类的神经元。这是令人鼓舞的，因为这意味着可能有更多类型的干细胞是我们没有的。我还不知道，也许有一些具备我们正在寻找的品质。另一方面，它使情况变得复杂，因为我们现在有更多的细胞需要排序。在我们这里描述的工作计划中，我们开始了解不同干细胞亚型在面临不同形式的损伤时可能出现的不同行为，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）或遗传形式的运动神经元疾病（脊髓运动神经元死亡，导致瘫痪）。我们将通过基因操纵老鼠，用荧光标记一种干细胞亚型或另一种干细胞亚型来做到这一点，这样我们就可以在完整的大脑中分别跟踪它们的行为。荧光标记还允许我们在培养皿中分别纯化和研究它们。

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.