Cellular hierachy of ER- breast cancers in different ethnic groups

描述(申请人提供)：正常干细胞和至少部分癌细胞都必须能够自我更新。自我更新的正常干细胞和自我更新的癌细胞之间的区别在于，与正常干细胞不同，在正常干细胞中，组织中的干细胞总数受到高度调控，超出正常水平的扩张受到遗传程序的限制[6]，而癌症中的自我更新细胞会持续扩张，从而导致肿瘤的发展。自我更新的癌细胞有两种可能的来源。首先，癌症可能源于正常干细胞，这些干细胞已经失去了自我更新的基因约束。其次，癌症可能是由具有自我更新能力的祖细胞引起的。我们的实验室已经使用单细胞基因组学开始定义正常人类乳腺上皮和新生乳腺肿瘤的细胞层次。在这项资助中，我们将使用这项技术来比较不同种族的ER-、PR-、ERB-B2-(三阴性)乳腺肿瘤的细胞层次结构与非正常乳腺上皮中发现的细胞类型。这一知识可能会为乳腺癌的治疗带来新的见解。以下具体目标将针对这些目标。 具体目标#1：使用单细胞基因组学技术来确定正常人类上皮的细胞层次。 具体目的#2：利用单细胞基因组学技术了解ER-PR-ERB-B2-(三阴性，基底细胞)乳腺癌在不同种族群体中的细胞层次结构。

DESCRIPTION (provided by applicant): Both normal stem cells and at least some of the cancer cells must be able to self renew. The difference between a self renewing normal stem cell and a self renewing cancer cell is that unlike normal stem cells in which the total number of stem cells in a tissue is highly regulated and expansion beyond the normal level is restricted by genetic programs [6], there is a continuous expansion of self renewing cells in cancer resulting in the development of a tumor. There are 2 possible cells of origin for the self renewing cancer cells. First, it is possible that the cancers arise from normal stem cells that have lost the genetic constraints on self renewal. Next, it is possible that cancers arise from progenitor cells that have acquired the ability to self renew. Our laboratories have used single cell genomics to begin to define the cellular hierarchy of the normal human breast epithelium and de novo breast tumors. In this grant, we will use this technology in order to compare the cellular hierarchies of ER-,PR-, ERB-B2- (triple negative) breast tumors of different ethnicities to the cell types found in nonnal breast epithelium. This knowledge may lead to new insights into the treatment of breast cancer. The following specific aims will address those goals. Specific Aim # 1: To use single cell genomics technology to define the cellular hierarchy of normal human epithelium. Specific Aim #2: To use single cell genomics technology to understand the cellular hierarchy of ER-PR-ERB-B2- (triple negative, basal cell) breast cancer in different racial groups.