Cell Competition: Genes That Drive Tissue Replacement

描述（由申请人提供）：再生医学的一条途径将涉及引入干细胞或祖细胞来修复受损组织。最大限度地发挥这些细胞的作用是很重要的。细胞对生长和生存因子的竞争可以极大地影响不同细胞群体的贡献。最近的研究表明，积极竞争的细胞会杀死、消灭和取代其他细胞，使用先前已知的在凋亡尸体吞噬和神经元重塑中重要的基因活性。这些基因在细胞竞争中的作用是偶然发现的，目前还不知道还有哪些基因和途径是必要的，或者是充分的，以促进细胞竞争的成功。前向遗传筛选是一种识别在细胞竞争中成功所需的基因的手段，但一般来说不是生长所需的基因，作为一种公正鉴定基因和途径的手段，这些基因和途径可能被操纵，以促进组织再生和再生，而不会导致癌症或其他生长障碍。

DESCRIPTION (provided by applicant): One route to regenerative medicine will involve introduction of stem or progenitor cells to repair damaged tissues. Maximizing the contribution of such cells will be important. Cell competition for growth and survival factors can greatly affect the contribution of distinct cell populations. Recent work shows that cells that compete actively kill, eliminate, and replace other cells, using activity of genes previously known to be important in apoptotic corpse engulfment and neuronal remodeling. The roles of these genes in cell competition has been uncovered serendipitously, and it is not known what other genes and pathways are necessary, or sufficient, to promote success in cell competition. A forward genetic screen is proposed as a means to identify genes that are required for success in cell competition, but not required for growth in general, as a means to the unbiased identification of genes and pathways that might be manipulated in order to promote tissue repopulation and regeneration without promoting cancer or other growth disorders. Public Health Relevance: When introducing stem or progenitor cells to repair damaged tissues, maximizing the contribution of such cells will be desirable. Recent studies of cells competing within tissues indicate that activities of specific genes can greatly affect the relative capacity of cells to contribute to tissues in vivo. It is proposed that genes with roles in cell competition can be identified by genetic screening, so that their potential use in regenerative medicine may be assessed.