Morales Jemery, Quintero Plancarte Gabriel, Hua Lisa
Biology Department, Sonoma State University, Rohnert Park, CA 94928.
bioRxiv. 2025 Mar 17:2025.03.15.643486. doi: 10.1101/2025.03.15.643486.
During mitosis, pairing of homologous chromosomes can be detrimental and has been correlated with gene misregulation, chromosomal aberrations, and various pathological diseases. We previously demonstrated that homologous chromosomes are spatially segregated, or antipaired, in neonatal human endothelial cells at metaphase/anaphase, which may help prevent abnormal recombination. However, it is unclear if this antipairing persists in adult endothelial cells. To test whether the antipairing, or one homolog per nuclear hemisphere motif, is conserved in adult endothelial cells, we examined human aortic endothelial cells at metaphase. Using ImmunoFISH and high-resolution confocal microscopy to visualize the chromosomes and centrosomes, we found that small homologous chromosomes 13, 15, 17, 19, 21, 22, and the sex chromosomes, XY, exhibit a loss of spatial segregation in human adult aortic endothelial cells. In contrast, fewer adult endothelial cells showed a loss of segregation for the larger chromosomes 1, 4, and XX, suggesting a gradual decline in the fidelity of spatial segregation of homologous chromosomes. Notably, we observed a higher frequency of abnormal pairing in both small and large chromosomes in adult aortic endothelial cells as compared to neonatal umbilical vein endothelial cells. These findings suggest that mechanisms governing chromosome antipairing may decline with aortic endothelial cell age, leading to increased susceptibility to abnormal pairing and cardiovascular disease.
在有丝分裂过程中，同源染色体配对可能是有害的，并且与基因调控异常、染色体畸变及各种病理疾病相关。我们之前证明，在新生儿人类内皮细胞的中期/后期，同源染色体在空间上是分离的，即反配对，这可能有助于防止异常重组。然而，目前尚不清楚这种反配对在成年内皮细胞中是否持续存在。为了测试反配对，即每个核半球一个同源染色体基序，在成年内皮细胞中是否保守，我们检查了中期的人类主动脉内皮细胞。使用免疫荧光原位杂交（ImmunoFISH）和高分辨率共聚焦显微镜观察染色体和中心体，我们发现人类成年主动脉内皮细胞中，小的同源染色体13、15、17、19、21、22以及性染色体XY，在空间上失去了分离。相比之下，较少的成年内皮细胞显示较大的染色体1、4和XX失去分离，这表明同源染色体空间分离的保真度逐渐下降。值得注意的是，与新生儿脐静脉内皮细胞相比，我们观察到成年主动脉内皮细胞中小染色体和大染色体的异常配对频率更高。这些发现表明，控制染色体反配对的机制可能会随着主动脉内皮细胞年龄的增长而衰退，导致异常配对和心血管疾病的易感性增加。
