Stem and progenitor cells of the postnatal CNS

出生后中枢神经系统的干细胞和祖细胞

• 批准号: G0800575/1
• 负责人: William Richardson
• 金额: $ 238.87万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0800575%2F1
• 关键词: Stem; progenitor; cells; postnatal; CNS

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.

最近，神经生物学的最大惊喜之一是意识到，成年大脑中有许多干细胞的口袋，它们在啮齿动物和人类中都会不断产生新的神经元。大多数？成人？神经元填充了嗅球（识别气味所需的大脑结构）和海马（一种涉及在放置地方和事件的记忆的神秘结构）。我们仍然对新神经元的精确作用处于黑暗状态。然而，由于干细胞可以在正常条件下产生某些类型的神经元，因此它们可能具有产生神经元来替代因损伤或神经退行性疾病（如帕金森氏症或阿尔茨海默氏症）而丧失的神经元的潜力更大的潜力。这是一个具有挑战性的想法，因为据我们所知，干细胞通常不会使这些疾病中被破坏的神经元类型。问题是，如果我们能学习如何调整，他们是否有潜力使我们想要的神经元？他们？我们和其他人最近发现，健康大脑中不仅有一种干细胞，而且有几个可能具有略有不同的特性，并且专门从事嗅球中的不同类型的神经元。这是令人鼓舞的，因为它意味着我们可能还不知道更多类型的干细胞，也许有些具有我们正在寻找的特性。另一方面，它使图片复杂化，因为我们现在有更多的单元格可以整理。在工作计划中，我们在这里描述了我们开始了解不同形式的损害时，我们可能会从不同的干细胞亚型中期望的不同行为，例如缺血（血液供应中断（例如中风中的血液供应）或脱髓鞘发生）或脱髓鞘（在神经纤维周围的绝缘纤维中的损失，例如在多发性状态下发生的跨性型NEURON疾病），或者是在多发性疾病中发生的，是属于多发性疾病的疾病。瘫痪。我们将通过遗传操纵小鼠来标记一个干细胞亚型或另一个带有荧光标签的小鼠，以便我们可以在完整的大脑中分别遵循它们的行为。