Advancing therapeutics by exploiting single cell functional analysis

人体含有数万亿个不同谱系和功能的细胞，但所有细胞都来自同一个受精胚胎。了解它们的相似性和差异（细胞的“异质性”）是设计所有需要针对体内特定稀有细胞的疗法的巨大障碍。越来越需要分析不同细胞群如何产生的基础，以及将它们标记为不同的一组特征（生物标志物）。这可能是由于这些细胞的稳定变化或动态变化导致细胞特性反复波动。重要的是要了解这些可能的情况何时以及是否适用。这需要新的技术进步，可以更好地分析这些细胞，以显示这种变异的基础，并识别，鉴定和操纵疾病过程中的重要细胞群。（称为循环肿瘤细胞，或CTC），这些细胞会产生耐药性癌症，如某些肺癌，并导致复发，和特定的干细胞（具有自我更新或分化潜力的细胞），能够使受损组织如肌肉、关节、皮肤和血管再生。为了在我们设计能够特异性靶向这些特定“祖细胞”群体的疗法的能力上实现“逐步推进”，我们将在曼彻斯特大学建立一个开创性的单细胞研究中心（SCRC）。通过对最新单细胞技术的开发和创新，它将包括一个通用的集成管道，从临床样本的接收，到每个样本中单个靶细胞的识别和表征，再到针对这些特定细胞的治疗设计。通过这种方式，它将加快对一些最具挑战性的疾病和人类退行性疾病的基于细胞和“个性化”治疗的进展。我们对SCRC的愿景是，在最初的3-5年内，细胞“签名”将被获得并验证，这将成为强大的新“精确”治疗的基础。因此，鉴于患有退行性疾病和无法治愈的癌症的人数迅速增加，建立SCRC特别及时。

The human body contains trillions of cells of many different lineages and functions, yet all are descended from the same fertilised embryo. Understanding their similarities and differences (cell 'heterogeneity') is a huge barrier to the design of all therapies that need to target particular rare cells within the body. There is an increasing need to analyse the basis of how varying groups of cells arise, as well as the set of characteristics (biomarkers) that mark them out as being different. This may be due to stable changes, or dynamic changes in these cells that lead to repeatedly fluctuating cell characteristics. It is important to understand when and whether each of these possible situations applies. This requires new technical advances that can better analyse these cells to show the basis of this variation and to identify, characterise and manipulate important groups of cells that underly disease processes.We focus on characterising a group of rare cells (called circulating tumour cells, or CTCs) that give rise to drug-resistant cancers such as certain lung cancers and lead to relapse, and specific stem cells (cells with the potential to self-renew or differentiate) that can enable the regeneration of damaged tissues such as muscle, joints, skin and blood vessels.To achieve a 'step-advance' in our ability to design therapies that can specifically target such specific 'progenitor' cell populations, we will establish a ground-breaking Single Cell Research Centre (SCRC) at the University of Manchester. Exploiting and innovating in the very latest single cell technologies, it will comprise a common integrated pipeline from receipt of clinical samples, to identification and characterisation of single target cells within each sample, to the design of treatments that target these specific cells. In this way, it will expedite progress to cell-based and 'personalised' treatments for some of the most challenging diseases and degenerative conditions of man. Our vision for SCRC is that, within the first 3-5 years, the cellular 'signatures' will have been obtained and verified that will form the basis for potent new 'precision' therapies. The establishment of SCRC is thus particularly timely, given the rapidly growing numbers of people with degenerative conditions and untreatable cancers.