Advancing therapeutics by exploiting single cell functional analysis

人体包含数以万亿计的不同血统和功能的细胞，但所有细胞都来自同一个受精胚胎。对于所有需要针对体内特定稀有细胞的治疗方法的设计来说，了解它们的异质性(细胞‘异质性’)是一个巨大的障碍。人们越来越需要分析不同的细胞组如何产生的基础，以及将它们标记为不同的一组特征(生物标记物)。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。了解这些可能的情况何时适用以及是否适用，这一点很重要。这需要新的技术进步，能够更好地分析这些细胞，以显示这种变异的基础，并识别、表征和操纵疾病过程中的重要细胞组。我们专注于表征一组稀有细胞(称为循环肿瘤细胞，简称CTCs)和特定干细胞(具有自我更新或分化能力的细胞)，这些细胞可导致某些肺癌等耐药癌症并导致复发，而特定干细胞可使受损组织(如肌肉、关节、皮肤和血管)再生。为了实现我们在设计治疗方法方面的“进步”，我们可以专门针对这些特定的“祖细胞”群体。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)。利用和创新最新的单细胞技术，它将包括一个共同的集成管道，从接收临床样本，到识别和表征每个样本中的单个靶细胞，再到针对这些特定细胞的治疗设计。通过这种方式，它将加快对人类一些最具挑战性的疾病和退化性疾病进行基于细胞的个性化治疗的进展。我们对SCRC的愿景是，在最初的3-5年内，细胞‘签名’将被获得并得到验证，这将形成强有力的新‘精确’疗法的基础。因此，鉴于患有退化性疾病和无法治疗的癌症的人数迅速增加，成立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.