RNAseq analysis of whole Guts over expressing LaminDm0 or GFP in Enterocytes

A hallmark of aging-related disease such as neurodegeneration, metabolic disorders, and cancer is the inability of differentiated cells to maintain their identity. In a search for identity regulators, we found that transcription factor Hey supervises the identity of differentiated enterocytes (ECs) in the adult Drosophila midgut. Lineage tracing of ECs established that Hey-deficient ECs lose differentiated identity, are unable to maintain their unique nuclear organization, and exhibit pathological reprograming. Orchestrating this organization, Hey specifies and maintains enhancer activity and nuclear lamins expression, remodeling nuclear architecture from a stem-cell configuration into a differentiated one. Moreover, maintaining this configuration of nuclear lamins is key for cell identity, and lamin misexpression overrides cell identities. At the tissue level, loss of Hey or expression of stem cell-related lamin (LamDm0) in ECs resulted in mis-differentiation, impaired epithelial integrity, and reduced organismal survival. Thus, a single transcription factor concomitantly supervises chromatin and nuclear organization, safeguarding cell identity mRNA of 4 biological repeats of Drosophila control (UAS>GFP) guts and 4 biological repeats of Guts expressing UAS-LamDm0 in EC (enterocytes).