Megakaryocyte endomitosis is a failure of late cytokinesis related to defects in the contractile ring and Rho/Rock signaling
Megakaryocyte endomitosis is a failure of late cytokinesis related to defects in the contractile ring and Rho/Rock signaling
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DOI：
10.1182/blood-2008-03-144956
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发表时间：
2008-10-15
期刊：
影响因子：
20.3
通讯作者：
Chang, Yunhua
中科院分区：
文献类型：
--
作者：
Lordier, Larissa;Jalil, Abdelali;Chang, Yunhua
巨核细胞（MK）是产生血小板的天然多倍体细胞。多倍化发生在细胞内有丝分裂，这是一个被认为是不完全的有丝分裂在后期中止的过程。在这里，我们使用延时共聚焦视频显微镜来可视化原代人类巨核细胞的核内有丝分裂过程。我们的研究结果表明，从有丝分裂到内有丝分裂的转换对应于胞质分裂的晚期失败，伴随着2个子细胞的向后运动。内有丝分裂MK的纺锤体未见异常。存在沟形成，但收缩环异常，因为缺乏非肌肉肌球蛋白IIA的积累。此外，在分裂末期偶极核内有丝分裂MK中观察到细胞伸长缺陷。RhoA和F-肌动蛋白部分集中在开沟的网站。Rho/Rock通路的抑制引起中间区F-肌动蛋白的消失和MK倍性水平的增加。这种抑制与一个更明显的缺陷，在沟的形成，以及在纺锤体伸长。我们的研究结果表明，胞质分裂的后期失败负责的有丝分裂过程中的Rho/Rock途径激活的部分缺陷。
Megakaryocyte (MK) is the naturally polyploid cell that gives rise to platelets. Polyploidization occurs by endomitosis, which was a process considered to be an incomplete mitosis aborted in anaphase. Here, we used time-lapse confocal video microscopy to visualize the endomitotic process of primary human megakaryocytes. Our results show that the switch from mitosis to endomitosis corresponds to a late failure of cytokinesis accompanied by a backward movement of the 2 daughter cells. No abnormality was observed in the central spindle of endomitotic MKs. A furrow formation was present, but the contractile ring was abnormal because accumulation of nonmuscle myosin IIA was lacking. In addition, a defect in cell elongation was observed in dipolar endomitotic MKs during telophase. RhoA and F-actin were partially concentrated at the site of furrowing. Inhibition of the Rho/Rock pathway caused the disappearance of F-actin at midzone and increased MK ploidy level. This inhibition was associated with a more pronounced defect in furrow formation as well as in spindle elongation. Our results suggest that the late failure of cytokinesis responsible for the endomitotic process is related to a partial defect in the Rho/Rock pathway activation.