Department of Biology, The Johns Hopkins University, Baltimore, MD, USA.
Howard Hughes Medical Institute, Baltimore, MD, USA.
EMBO Rep. 2023 Jul 5;24(7):e56404. doi: 10.15252/embr.202256404. Epub 2023 May 31.
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.
我们报告称，在果蝇肠道干细胞（ISCs）分裂过程中，旧的和新合成的组蛋白 H3 和 H4 是不对称分配的。此外，有丝分裂后细胞对中旧和新 H3 和 H4 的遗传模式与 Delta（一种重要的细胞命运基因）的不同表达模式相关。为了理解这一现象的生物学意义，我们表达了一种突变体 H3T3A，以破坏不对称的组蛋白遗传。在这种情况下，我们观察到 Delta 对称细胞对的增加和过表达的 ISC 样、Delta 阳性细胞。单细胞 RNA-seq 分析进一步表明，H3T3A 的表达破坏了 ISC 的分化。总之，我们的结果表明，不对称的组蛋白遗传可能有助于在体干细胞谱系中建立不同的细胞身份，这与之前在果蝇雄性生殖干细胞中的发现一致。
