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

正常人脑和脊髓的少突胶质细胞有何异质性？

• 批准号: MR/S035915/1
• 负责人: Anna Williams
• 金额: $ 57.64万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS035915%2F1
• 关键词: How; heterogeneous; oligodendroglia; normal; human

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.

人类大脑的复杂性可能是我们作为人类的定义，而大脑的少突胶质细胞在维持这一点方面至关重要。这些细胞延伸其细胞膜的突起，将绝缘的髓鞘包裹在神经纤维周围，使电脉冲能够沿着神经快速传播，它们也滋养了下面的神经，帮助它健康地生存。这种髓鞘形成的过程主要发生在人类出生后，并允许婴儿正常发育成成人。然而，由于基因缺陷或早产，它可以在出生时被破坏，在成年期的疾病，如多发性硬化症和老年，无论是在正常老化，或在其他神经退行性疾病。我们曾经认为所有少突胶质细胞非常相似，但我们现在知道，它们可能存在不同的亚型，也许取决于它们来自哪里的发展，它们存在于大脑和脊髓中，并取决于人类的年龄和性别。它们也可能改变疾病的类型。我们称之为异质性，确定细胞差异的最佳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（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它们的相似性和差异性，从而以客观的方式进行数千次比较。然后，我们可以尝试使用标记单个RNA分子的技术来确认计算机的预测，使用抗体识别它们在哪些细胞中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，这些组织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，然后研究其相似性和差异性。这将使我们能够识别行为不同的少突胶质细胞亚型，并且可能更容易受到男性和女性疾病或衰老的影响。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人进行比较，并以一种非常具体的方式开发针对少突胶质细胞亚型的治疗方法，以帮助疾病。这将是人类细胞图谱的一部分，所有数据将被存储并汇集来自世界各地的研究人员，允许免费访问和合作，其目的是改善和加速生物和医学研究。

项目成果

The Lysosomal Transcription Factor TFEB Represses Myelination Downstream of the Rag-Ragulator Complex.

• DOI: 10.1016/j.devcel.2018.10.003
• 发表时间: 2018-11-05
• 期刊: Developmental cell
• 影响因子: 11.8
• 作者: Meireles AM;Shen K;Zoupi L;Iyer H;Bouchard EL;Williams A;Talbot WS
• 通讯作者: Talbot WS

Oligodendroglial Heterogeneity in Neuropsychiatric Disease.

• DOI: 10.3390/life11020125
• 发表时间: 2021-02-06
• 期刊: Life (Basel, Switzerland)
• 作者: Bøstrand SMK;Williams A
• 通讯作者: Williams A

New oligodendrocytes exhibit more abundant and accurate myelin regeneration than those that survive demyelination

• DOI: 10.1101/2020.05.22.110551
• 发表时间: 2020-05
• 期刊: Nature neuroscience
• 影响因子: 25
• 作者: Sarah A. Neely;Jill M Williamson;Anna Klingseisen;Lida Zoupi;J. Early;Anna C. Williams;D. Lyons