RESEARCH ARTICLE The transcription factor Hey and nuclear lamins specify and maintain cell identity Naama Flint Brodsly1†, Eliya Bitman-Lotan1†, Olga Boico1, Adi Shafat1, Maria Monastirioti2, Manfred Gessler3, Christos Delidakis2, Hector Rincon-Arano4, Amir Orian1* 1Rappaport Research Institute and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; 2Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology - Hellas (FORTH), Heraklion, Greece; 3Biocenter of Developmental Biochemistry, University of Wu¨ rzburg, Wu¨ rzburg, Germany; 4Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States Abstract The inability of differentiated cells to maintain their identity is a hallmark of age- related diseases. We found that the transcription factor Hey supervises the identity of differentiated enterocytes (ECs) in the adult Drosophila midgut. Lineage tracing established that Hey-deficient ECs are unable to maintain their unique nuclear organization and identity. To supervise cell identity, Hey determines the expression of nuclear lamins, switching from a stem-cell lamin configuration to a differentiated lamin configuration. Moreover, continued Hey expression is required to conserve large-scale nuclear organization. During aging, Hey levels decline, and EC identity and gut homeostasis are impaired, including pathological reprograming and compromised gut integrity. These phenotypes are highly similar to those observed upon acute targeting of Hey or perturbation of lamin expression in ECs in young adults. Indeed, aging phenotypes were suppressed by continued expression of Hey in ECs, suggesting that a Hey-lamin network *For correspondence: safeguards nuclear organization and differentiated cell identity.
[email protected] DOI: https://doi.org/10.7554/eLife.44745.001 †These authors contributed equally to this work Competing interests: The authors declare that no Introduction competing interests exist.