The transcription factor Hey and nuclear lamins specify and maintain cell identity

eLife

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[1] Biocenter of Developmental Biochemistry, University of Würzburg, Würzburg, Germany;Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States;Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology - Hellas (FORTH), Heraklion, Greece;Rappaport Research Institute and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel;

关键词: cell identity;    gene regulation;    nuclear organization;    hey;    lamin;    ageing;    D. melanogaster;   

DOI  :  10.7554/eLife.44745

来源: publisher

【 摘 要 】

10.7554/eLife.44745.001The 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 safeguards nuclear organization and differentiated cell identity.

【 授权许可】

CC BY