Clone wars: the emerging role of telomerase in stem cell competition
Sep. 16, 2020 9:30 - 10:30
Category
Seminar
Place
Other
Venue
Online seminar
Speaker
Kazuteru Hasegawa
Affiliation
Stanford Cancer Institute, Stanford University (Laboratory of Dr. Steven E. Artandi)
Poster
Summary
Tissue development and homeostasis are shaped by cell competition, a mechanism for culling unfit cells. During carcinogenesis, mutations in cancer genes confer a competitive growth advantage through an analogous process. Here, we show that the telomerase reverse transcriptase (TERT) is required for competitive clone formation in spermatogonial stem cells (SSCs). Using competitive lineage-tracing from the endogenous Tert locus, we find that TERT-expressing SSCs yield long-lived clones, but that selective TERT-deletion in SSCs disrupts clone formation by promoting differentiation. This requirement for TERT is independent of catalytic activity and the canonical telomerase complex. Loss of TERT induces a genome-wide reduction in open chromatin and causes reduced activity of the MYC oncogene. Transgenic expression of MYC in TERT-deleted SSCs rescues competitive clone formation. These data reveal an unexpected role for TERT in promoting stem cell competition, uncover a genetic link between TERT and MYC, and suggest new means by which TERT may delay aging and drive carcinogenesis.
Host
Tomoya Kitajima