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

Autor:	Flint Brodsly N; Rappaport Research Institute and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel., Bitman-Lotan E; Rappaport Research Institute and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel., Boico O; Rappaport Research Institute and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel., Shafat A; Rappaport Research Institute and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel., Monastirioti M; Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology - Hellas (FORTH), Heraklion, Greece., Gessler M; Biocenter of Developmental Biochemistry, University of Würzburg, Würzburg, Germany., Delidakis C; Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology - Hellas (FORTH), Heraklion, Greece., Rincon-Arano H; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States., Orian A; Rappaport Research Institute and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2019 Jul 16; Vol. 8. Date of Electronic Publication: 2019 Jul 16.
DOI:	10.7554/eLife.44745
Abstrakt:	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 safeguards nuclear organization and differentiated cell identity. Competing Interests: NF, EB, OB, AS, MM, MG, CD, HR, AO No competing interests declared (© 2019, Flint Brodsly et al.)
Databáze:	MEDLINE
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