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Transposable elements (TEs) play a significant role in evolution, contributing to genetic variation. However, TE mobilization in somatic cells is not well understood. Here, we address the prevalence of transposition in a somatic tissue, exploiting the Drosophila midgut as a model. Using whole‐genome sequencing of in vivo clonally expanded gut tissue, we have mapped hundreds of high‐confidence somatic TE integration sites genome‐wide. We show that somatic retrotransposon insertions are associated with inactivation of the tumor suppressor Notch, likely contributing to neoplasia formation. Moreover, applying Oxford Nanopore long‐read sequencing technology we provide evidence for tissue‐specific differences in retrotransposition. Comparing somatic TE insertional activity with transcriptomic and small RNA sequencing data, we demonstrate that transposon mobility cannot be simply predicted by whole tissue TE expression levels or by small RNA pathway activity. Finally, we reveal that somatic TE insertions in the adult fly intestine are enriched in genic regions and in transcriptionally active chromatin. Together, our findings provide clear evidence of ongoing somatic transposition in Drosophila and delineate previously unknown features underlying somatic TE mobility in vivo. SYNOPSIS: Technical challenges with detecting somatic transposable element (TE) insertions have hampered determination of the extent of somatic transposition in adult tissues. The current study provides genomic evidence for endogenous retrotransposition events in the Drosophila intestine and uncovers underlying features of somatic TE mobility in vivo. A combination of short‐read and long‐read DNA sequencing reveals tissue‐specific differences in genome‐wide retrotransposon mobility.Somatic TE insertions in the gut are enriched in genic regions, as well as in active, enhancer‐like chromatin.TE insertions in the tumor suppressor gene Notch in intestinal stem cells may contribute to the formation of gut neoplasia. [ABSTRACT FROM AUTHOR]

How terminal cell fates are specified in dynamically renewing adult tissues is not well understood. Here we explore terminal cell fate establishment during homeostasis using the enteroendocrine cells ( EEs) of the adult Drosophila midgut as a paradigm. Our data argue against the existence of local feedback signals, and we identify Numb as an intrinsic regulator of EE fate. Our data further indicate that Numb, with alpha-adaptin, acts upstream or in parallel of known regulators of EE fate to limit Notch signaling, thereby facilitating EE fate acquisition. We find that Numb is regulated in part through its asymmetric and symmetric distribution during stem cell divisions; however, its de novo synthesis is also required during the differentiation of the EE cell. Thus, this work identifies Numb as a crucial factor for cell fate choice in the adult Drosophila intestine. Furthermore, our findings demonstrate that cell-intrinsic control mechanisms of terminal cell fate acquisition can result in a balanced tissue-wide production of terminally differentiated cell types. [ABSTRACT FROM AUTHOR]

The Drosophila adult posterior midgut has been identified as a powerful system in which to study mechanisms that control intestinal maintenance, in normal conditions as well as during injury or infection. Early work on this system has established a model of tissue turnover based on the asymmetric division of intestinal stem cells. From the quantitative analysis of clonal fate data, we show that tissue turnover involves the neutral competition of symmetrically dividing stem cells. This competition leads to stem-cell loss and replacement, resulting in neutral drift dynamics of the clonal population. As well as providing new insight into the mechanisms regulating tissue self-renewal, these findings establish intriguing parallels with the mammalian system, and confirm Drosophila as a useful model for studying adult intestinal maintenance. [ABSTRACT FROM AUTHOR]