How heterogeneous are oligodendroglia from normal human brain and spinal cord?

人类大脑的复杂性可能定义了我们作为人类，而大脑的少突胶质细胞在维持这一点上至关重要。这些细胞延伸它们的细胞膜，将绝缘的髓鞘包裹在神经纤维周围，允许电脉冲沿着神经快速传播，它们也滋养底层的神经，帮助它健康地存活。这种髓鞘形成过程主要发生在人类出生后，并使婴儿正常发育为成年人。然而，在出生前后，由于基因缺陷或早产，在成年时患有多发性硬化症等疾病，在老年时，无论是正常衰老还是其他神经退行性疾病，它都可能被破坏。我们过去认为所有的少突胶质细胞都非常相似，但我们现在知道它们可能以不同的亚型存在，这可能取决于它们在发育过程中的来源，它们在大脑和脊髓中的位置，以及人类的年龄和性别。他们也可能改变自己的疾病类型。我们称之为异质性，确定细胞差异的最好方法是单独考虑它们。我们现在能够检查单个细胞中的RNA信息（它定义细胞的行为），将它们与其他单个细胞进行比较，并使用计算机程序找出这些细胞之间的相似和不同之处，从而以客观的方式进行数千次比较。然后，我们可以尝试用标记单个RNA分子的技术来证实计算机的预测，利用抗体来识别它们所在的细胞以及它们在脑组织中的位置。在这个项目中，我们将从人类死后的大脑和脊髓组织中提取少突胶质细胞，分别来自男性和女性婴儿，年轻人和老年人，来自两个不同的大脑区域和脊髓，检测每个少突胶质细胞中的rna，然后研究它们的异同。这将使我们能够识别行为不同的少突胶质细胞亚型，这些亚型在男性和女性中可能更容易受到疾病或衰老的影响。在未来，我们可以将患有其他少突胶质细胞疾病的人的少突胶质细胞与这些进行比较，并开发针对少突胶质细胞亚型的治疗方法，以一种非常特殊的方式来帮助治疗疾病。这将是人类细胞图谱的一部分，其中所有数据将被存储和汇集来自世界各地的研究人员，允许自由访问和合作，其目的是改善和加速生物和医学研究。

The intricacies of the human brain are probably what define us as human, and the oligodendrocytes of the brain are vital in maintaining this. These cells extend processes of their cell membrane to wrap insulating myelin sheaths around nerve fibres, allowing electrical impulses to travel quickly along nerves, and they also nourish the underlying nerve, helping it to survive healthily. This process of myelination happens mostly after birth in humans, and allows the normal development of a baby into an adult. However, it can be disrupted around birth, due to gene defects or premature birth, in adulthood in diseases such as multiple sclerosis and in old age, either in normal ageing, or in other neurodegenerative diseases.We used to consider all oligodendrocytes as very similar, but we now know that they are likely to exist as different subtypes, perhaps depending on where they came from in development, where they exist in the brain and spinal cord, and depending on the age and sex of the human. They may also change their type in disease. We call this heterogeneity, and the best way to determine how different cells are is to consider them individually. We are now able to examine the RNA messages (which define how a cell behaves) in individual cells, comparing them with other individual cells, and finding out how similar and how different these are using computer programs, allowing thousands of comparisons in an objective way. We can then try and confirm the computer's predictions using techniques to label single RNA molecules, identifying which cells they are in and where they are in brain tissue using antibodies.In this project, we will extract oligodendrocytes from human post mortem brain and spinal cord tissue from male and female babies, young adults and old adults, from two different brain regions and spinal cord, detect the RNAs in each individual oligodendrocyte and then study the similarities and differences. This will allow us to identify subtypes of oligodendrocytes that behave differently, and that might be more vulnerable to disease or ageing in males and females. In the future, we can then compare oligodendrocytes from people with other oligodendrocyte diseases with these, and develop therapies that target the subtype of oligodendrocytes to help the disease, in a very specific way.This will be part of the Human Cell Atlas where all data will be stored and pooled from researchers all around the world, allowing free access and collaboration, which the aim of improving and accelerating biological and medical research.