Transcriptional Heterogeneity Individual of Human Adipose Stromal Cells

描述（由申请人提供）：大多数成年组织在损伤或疾病后再生能力最低。这种再生潜力的缺乏在治疗广泛的疾病中提出了主要的临床挑战，包括中风、心肌梗死、骨缺损、脊髓损伤、糖尿病和肾衰竭。为了满足这种临床需求，再生医学的一个主要目标是使用干细胞来修复或替换受损或缺失的组织。基于干细胞的再生应用中最有前途的细胞类型之一是脂肪源性基质细胞（ASC），因为它们很容易从微创脂肪抽吸手术中大量分离，并且可以分化成几种不同的组织类型。许多研究人员已经证明，ASCs可以分化成几种组织类型，并提出使用这些细胞进行组织再生;这一领域仍处于起步阶段。尚未解决的主要挑战之一是干细胞的异质性。虽然已知干细胞群体是异质的，但这种异质性的功能后果尚未完全阐明。在干细胞有效地用于治疗应用之前，必须克服干细胞内不确定的异质性问题。理解这种异质性的第一步是阐明这些复杂细胞的基因表达谱。为了满足这一需求，我们开发了一种新的高分辨率，高通量的方法来分析多个基因在多个单个细胞中的同时表达。该提议的中心假设是，人脂肪来源的基质细胞内的转录异质性可以在单细胞水平上定义，这将允许选择具有最大潜力的细胞亚组用于基于细胞的疗法。

DESCRIPTION (provided by applicant): Most adult tissues have minimal capacity for regeneration following injury or disease. This lack of regenerative potential presents a major clinical challenge in treating a broad range of diseases, including stroke, myocardial infarction, bone defects, spinal cord injury, diabetes, and kidney failure. To address this clinical need, a major goal of regenerative medicine is to use stem cells to repair or replace damaged or missing tissue. One of the most promising cell types for stem cell-based regenerative applications is adipose-derived stromal cells (ASCs), as they are readily isolated in large numbers from minimally invasive lipoaspiration procedures and can differentiate into several different tissue types. Many investigators have demonstrated that ASCs can differentiate into several tissue types and have proposed using these cells for tissue regeneration; this field is still in its infancy. On of the major challenges that has not been solved is the heterogeneous nature of stem cells. While stem cell populations are known to be heterogeneous, the functional consequences of this heterogeneity have not been fully elucidated. The problem of undefined heterogeneity within stem cells must be overcome before they can be used effectively for therapeutic applications. The first step to understand this heterogeneity is to elucidate the gene expression profiles of these complex cells. To address this need, we have developed a novel high resolution, high-throughput method to analyze the concurrent expression of multiple genes across multiple individual cells. The central hypothesis of this proposal is that the transcriptional heterogeneity within human adipose derived stromal cells can be defined on the single cell level, which will allow selection of cell subgroups with the greatest potential for use in cell-based therapies.