pTa-controlled reporter to identify lymphoid precursor

pTa 控制的报告基因识别淋巴前体

• 批准号: 7172234
• 负责人: HARALD VON BOEHMER
• 金额: $ 40.53万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2008-07-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7172234
• 关键词: Adult; Bone Marrow; Cell surface; Cells; Clinical; Commit; Data; Development; Genes; Genetic Enhancer Element; Growth; Lymphoid; Lymphopoiesis; Myeloid Cells; Pluripotent Stem Cells; Process; Reporter; Reporter Genes; Role; Staging; Stem cells; T-Lymphocyte; Transplantation; fetal; interest; promoter; transcription factor

The development of lymphoid lineages from pluripotent stem cells is a poorly understood process. The identification of lymphoid committed precursors is not only of academic but also of clinical interest because of their faster immunorestorative potential when compared to hemopoietic stem cells (HSC) after transplantation into immunodeficient hosts. Previous analysis of the expression of the pre-TCRa (pTa) chain, which forms the pre-TCR in association with the TCRb chain, has shown its presence in precursors of T cells but not in pluripotent hemopoietic stem cells. This suggests that expression of the pTa gene marks lymphoid precursors. Therefore, we propose to isolate lymphoid precursors with the aid of reporter genes that are controlled by pTa promoter and enhancer elements. Our initial data indicate that such reporters can be expressed in lymphoid committed precursors in the bone marrow that are able to generate all lymphoid lineages but no myeloid cells. We propose to subdivide the reporter gene expressing cells by a variety of cell surface molecules that are involved in and correlate with lymphoid development. We will then reveal the developmental potential of these subsets in order to generate a detailed picture of lymphoid commitment in fetal and adult lymphopoiesis and to identify branching points of the various lineages. We will further characterize developmental stages with regard to expression and essential role of transcription factors involved in lineage commitment.

从多能干细胞发育成淋巴样谱系是一个知之甚少的过程。的 淋巴定向前体细胞的鉴定不仅具有学术意义，而且具有临床意义 因为与造血干细胞（HSC）相比， 移植到免疫缺陷的宿主中。前TCR α（pTa）表达的先前分析 链，其与TCR b链结合形成前TCR，已显示其存在于前体中 而不是多能造血干细胞。这表明pTa基因的表达 标志着淋巴前体。因此，我们建议在报告基因的帮助下分离淋巴样前体细胞， 由pTa启动子和增强子元件控制的基因。我们的初步数据表明， 报告基因可以在骨髓中的淋巴定向前体中表达， 生成所有淋巴谱系但没有髓样细胞。我们建议细分报告基因 通过各种细胞表面分子表达细胞，这些细胞表面分子参与淋巴样细胞的形成并与淋巴样细胞的形成相关。 发展然后，我们将揭示这些子集的发展潜力，以产生一个 胎儿和成人淋巴细胞生成中淋巴定向的详细图像，并确定分支点 不同的血统。我们将进一步描述发育阶段的表达和 转录因子在谱系定型中的重要作用。