Old and newly synthesized histones are asymmetrically distributed in Drosophila intestinal stem cell divisions

Abstract

We report that preexisting (old) and newly synthesized (new) histones H3 and H4 are asymmetrically partitioned during the division of Drosophila intestinal stem cells (ISCs). Furthermore, the inheritance patterns of old and new H3 and H4 in postmitotic cell pairs correlate with distinct expression patterns of Delta, an important cell fate gene. To understand the biological significance of this phenomenon, we expressed a mutant H3T3A to compromise asymmetric histone inheritance. Under this condition, we observe an increase in Delta‐symmetric cell pairs and overpopulated ISC‐like, Delta‐positive cells. Single‐cell RNA‐seq assays further indicate that H3T3A expression compromises ISC differentiation. Together, our results indicate that asymmetric histone inheritance potentially contributes to establishing distinct cell identities in a somatic stem cell lineage, consistent with previous findings in Drosophila male germline stem cells.

Asymmetric division of stem cells and its cancer relevance

“…This biased segregation of histones is mediated by distinguishing the phosphorylation at threonine 3 of H3 (H3T3P) between pre-existing and newly synthesized H (Wooten et al 2019 ; Xie et al 2015 , 2017 ). The asymmetric partition of H3 and H4 histones also has been found in Drosophila intestinal stem cells (Zion et al 2023 ). In contrast, some studies argue that H2A and H2B histones are inherited symmetrically during the asymmetric division of GSCs (Wooten et al 2020 , 2019 ).…”