Cell Competition: Genes That Drive Tissue Replacement

描述（由申请人提供）：再生医学的一种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将是重要的。细胞对生长和存活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，细胞竞争积极杀死，消除，并取代其他细胞，利用以前已知的基因的活性是重要的凋亡尸体吞噬和神经元重塑。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促进细胞竞争成功所必需或足够的。正向遗传筛选被提出作为鉴定在细胞竞争中成功所需但一般生长不需要的基因的手段，作为无偏见地鉴定可能被操纵以促进组织再增殖和再生而不促进癌症或其他生长障碍的基因和途径的手段。 公共卫生相关性：当引入干细胞或祖细胞以修复受损组织时，最大化这些细胞的贡献将是期望的。最近对组织内细胞竞争的研究表明，特定基因的活性可以极大地影响细胞在体内对组织的贡献的相对能力。有人建议，在细胞竞争中发挥作用的基因可以通过遗传筛选来确定，从而可以评估它们在再生医学中的潜在用途。

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.