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

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.

Automated summary

We found that old and new histones H3 and H4 in Drosophila intestinal stem cells (ISCs) are asymmetrically partitioned during cell division. The inheritance patterns of these histones correlate with expression patterns of Delta gene, which is important for cell fate determination. By disrupting asymmetric histone inheritance, we observed an increase in symmetric cell pairs and overpopulation of ISC-like, Delta-positive cells, suggesting the role of asymmetric histone inheritance in establishing distinct cell identities in somatic stem cell lineage.