Gene Regulation of Cell Identity, Regenerative Medicine Program, Bellvitge Institute for Biomedical Research (IDIBELL), Barcelona, L'Hospitalet del Llobregat, Spain.
Program for Advancing Clinical Translation of Regenerative Medicine of Catalonia, P- CMR[C], Barcelona, L'Hospitalet del Llobregat, Spain.
Transcription. 2023 Jun-Oct;14(3-5):158-176. doi: 10.1080/21541264.2023.2295044. Epub 2024 Jan 23.
The development of highly parallel and affordable high-throughput single-cell transcriptomics technologies has revolutionized our understanding of brain complexity. These methods have been used to build cellular maps of the brain, its different regions, and catalog the diversity of cells in each of them during development, aging and even in disease. Now we know that cellular diversity is way beyond what was previously thought. Single-cell transcriptomics analyses have revealed that cell types previously considered homogeneous based on imaging techniques differ depending on several factors including sex, age and location within the brain. The expression profiles of these cells have also been exploited to understand which are the regulatory programs behind cellular diversity and decipher the transcriptional pathways driving them. In this review, we summarize how single-cell transcriptomics have changed our view on the cellular diversity in the human brain, and how it could impact the way we study neurodegenerative diseases. Moreover, we describe the new computational approaches that can be used to study cellular differentiation and gain insight into the functions of individual cell populations under different conditions and their alterations in disease.
高通量单细胞转录组学技术的发展极大地推动了我们对大脑复杂性的认识。这些方法被用于构建大脑及其不同区域的细胞图谱，并在发育、衰老甚至疾病过程中对每个区域中的细胞多样性进行编目。现在我们知道，细胞多样性远超之前的想象。单细胞转录组学分析表明，以前基于成像技术认为同质的细胞类型，根据包括性别、年龄和大脑内位置在内的几个因素而有所不同。这些细胞的表达谱也被用于了解细胞多样性背后的调控程序，并解析驱动它们的转录途径。在这篇综述中，我们总结了单细胞转录组学如何改变我们对人类大脑中细胞多样性的看法，以及它如何影响我们研究神经退行性疾病的方式。此外，我们还描述了可用于研究细胞分化的新计算方法，并深入了解不同条件下单个细胞群体的功能及其在疾病中的变化。
