Translational Core (Expression Core)

抽象-核心B 调节性B细胞(Bregs)的发育、功能和调节机制 炎性B效应细胞(BEFF)仍不清楚。到目前为止，对Bregs和Beff的研究一直具有挑战性 由于它们在临床标本中的数量很少，以及它们的异质性。然而，中国的发展 基因组学方法，如来自低输入样本的批量群体的RNA-Seq和单细胞RNA-Seq (scRNA-Seq)以及CRISPR-Cas9基因组编辑工具现在使这一目标触手可及。这个 博德研究所的转录和扰动核心将与PPG的所有三个项目合作，以 使用批量RNA-Seq、单细胞RNA-Seq和纳米串技术的图谱样本。我们将表演 计算分析，以生成电路模型并确定潜在的调节器和通路 Breg和Beff法规。我们将使用CRISPR-Cas9基因组编辑来测试这些预测模型 在原代细胞中的技术。核心将处理和分析所有项目的样本以及由此产生的 数据将在PPG的所有调查人员之间共享。总体而言，这些结果将带来更好的 了解Breg和Beff的生物学、正常功能及其在疾病中的作用。它还有可能领先于 为治疗自身免疫、癌症和移植排斥反应开辟新的途径。

ABSTRACT — CORE B The mechanisms underlying the development, function, and regulation of regulatory B-cells (Bregs) and inflammatory B-effector (Beff) cells remain obscure. To date, studies of Bregs and Beff have been challenging due to their small numbers in clinical samples as well as their heterogeneity. However, the development of genomic approaches, such as RNA-Seq of bulk populations from low-input samples and single-cell RNA-Seq (scRNA-Seq) as well as CRISPR–Cas9 genome editing tools, now put this goal within reach. The Transcriptional and Perturbation Core at the Broad Institute will collaborate with all three projects of the PPG to profile samples using bulk RNA-Seq, single-cell RNA-Seq, and NanoString technology. We will perform computational analysis to generate circuit models and identify potential regulators and pathways involved in Breg and Beff regulation. We will test these predictive models by using CRISPR-Cas9 genome editing technology in primary cells. The Core will process and analyze samples across all projects and the resulting data will be shared among all the investigators of the PPG. Overall, these results will lead to better understanding of Breg and Beff biology, normal function, and their role in disease. It may also potentially lead to new avenues for therapy for autoimmunity, cancer, and transplant rejection.