inStem (Institute for Stem Cell Science and Regenerative Medicine)

Department of Biotechnology
Department of Biotechnology
inStem (Institute for Stem Cell Science and Regenerative Medicine)

Developmental stage dominates cell-type identity and reveals a chromatin regulatory function for Rad50 in Drosophila.

Publication Type

Journal Article

Date of Publication

April 13, 2026

Journal

Nucleic acids research

Volume/Issue

54/7

ISSN

1362-4962

Cell types are fundamental units of metazoans, however, their definition remains a long-standing challenge. We here use high-throughput assays allowing for unprecedented resolution to analyze and compare the transcriptional landscapes of related and unrelated Drosophila cell types at larval and embryonic stages. Unexpectedly, all cell types share a stage-specific signature that is even stronger than the cell-specific one. Despite having distinct developmental origins and functions, neurons, glia, and hemocytes are more transcriptionally similar to one another within the same developmental stage than they are to the same cell type at different stages. This stage-specific signature is enriched for DNA repair genes at larval stage, particularly the MRN complex (Mre11-Rad50-Nbs). Loss of Rad50 disrupts histone modification patterns and causes inappropriate reactivation of embryonic gene expression programs in larval central nervous system (CNS), as revealed by transcriptomic and chromatin accessibility analyses. The identification of cell-specific and stage-specific signatures highlights a new dimension in the definition of cell identity and suggests a role for Rad50 in maintaining developmentally appropriate chromatin states.

Alternate Journal

Nucleic Acids Res

PubMed ID

41978263

PubMed Central ID

PMC13076223

Authors

Boutet T
Sakr R
Marzullo M
Goyal M
Cattenoz PB
Ciapponi L
Mukherjee T
Giangrande A

Keywords

DNA-Binding Proteins
Gene Expression Regulation
Drosophila melanogaster
Hemocytes
Larva
Developmental
Neuroglia
Central Nervous System
Histone Code
Animals
Drosophila
Drosophila Proteins
Neurons
Chromatin
DNA Repair