English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

The clonal expansion of mutant cells is hypothesized to be an important first step in cancer formation. To understand the earliest stages of tumorigenesis, a method to identify and analyze clonal expansion is needed. We have previously described transgenic Fluorescent Yellow Direct Repeat (FYDR) mice in which cells that have undergone sequence rearrangements (via homologous recombination events) express a fluorescent protein, enabling fluorescent labeling of phenotypically normal cells. Here, we develop an integrated one- and two-photon imaging platform that spans four orders of magnitude to permit rapid quantification of clonal expansion in the FYDR pancreas in situ. Results show that as mice age there is a significant increase in the number of cells within fluorescent cell clusters, indicating that pancreatic cells can clonally expand with age. Importantly, &gt;90% of fluorescent cells in aged mice result from clonal expansion, rather than de novo sequence rearrangements at the FYDR locus. The spontaneous frequency of sequence rearrangements at the FYDR locus is on par with that of other classes of mutational events. Therefore, we conclude that clonal expansion is one of the most important mechanisms for increasing the burden of mutant cells in the mouse pancreas.

Integrated one- and two-photon imaging platform reveals clonal expansion as a major driver of mutation load