RRC ID 57425
Author Flint Brodsly N, Bitman-Lotan E, Boico O, Shafat A, Monastirioti M, Gessler M, Delidakis C, Rincon-Arano H, Orian A.
Title The transcription factor Hey and nuclear lamins specify and maintain cell identity.
Journal Elife
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 safeguards nuclear organization and differentiated cell identity.
Volume 8
Published 2019-7-16
DOI 10.7554/eLife.44745
PII 44745
PMID 31310235
PMC PMC6634966
MeSH Aging / pathology Animals Basic Helix-Loop-Helix Transcription Factors / metabolism* Cell Differentiation* Drosophila / physiology* Drosophila Proteins / metabolism* Enterocytes / physiology* Lamins / metabolism* Stem Cells / physiology
IF 7.551
Times Cited 1
Drosophila 11194R-1 11194R-3