Bermudez Alexandra, Latham Zoe D, Ma Alex J, Bi Dapeng, Hu Jimmy K, Lin Neil Y C
Bioengineering Department, University of California Los Angeles, Los Angeles, CA, USA.
Department of Physics, Northeastern University, Boston, MA, USA.
Commun Biol. 2025 Feb 20;8(1):269. doi: 10.1038/s42003-025-07677-w.
Cell morphology heterogeneity is pervasive in epithelial collectives, yet the underlying mechanisms driving such heterogeneity and its consequential biological ramifications remain elusive. Here, we observed a consistent correlation between the epithelial cell morphology and nucleus morphology during crowding, revealing a persistent log-normal probability distribution characterizing both cell and nucleus areas across diverse epithelial model systems. We showed that this morphological diversity arises from asymmetric partitioning during cell division. Next, we provide insights into the impact of nucleus morphology on chromatin modifications. We demonstrated that constraining nucleus leads to downregulation of the euchromatic mark H3K9ac and upregulation of the heterochromatic mark H3K27me3. Furthermore, we showed that nucleus size regulates H3K27me3 levels through histone demethylase UTX. These findings highlight the significance of cell morphology heterogeneity as a driver of chromatin state diversity, shaping functional variability within epithelial tissues.
细胞形态异质性在上皮细胞群体中普遍存在，然而驱动这种异质性的潜在机制及其相应的生物学影响仍然难以捉摸。在这里，我们观察到在拥挤过程中上皮细胞形态与细胞核形态之间存在一致的相关性，揭示了一种持续的对数正态概率分布，该分布表征了不同上皮模型系统中细胞和细胞核的面积。我们表明，这种形态多样性源于细胞分裂过程中的不对称分配。接下来，我们深入探讨了细胞核形态对染色质修饰的影响。我们证明，限制细胞核会导致常染色质标记H3K9ac的下调和异染色质标记H3K27me3的上调。此外，我们表明细胞核大小通过组蛋白去甲基化酶UTX调节H3K27me3水平。这些发现突出了细胞形态异质性作为染色质状态多样性驱动因素的重要性，塑造了上皮组织内的功能变异性。
