Cell Competition: Genes That Drive Tissue Replacement

[unreadable] 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. [unreadable] [unreadable] 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. [unreadable] [unreadable] [unreadable]