Perez-Terzic Carmen, Behfar Atta, Méry Annabelle, van Deursen Jan M A, Terzic Andre, Pucéat Michel
Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Mayo Foundation, Rochester, Minn, USA.
Circ Res. 2003 Mar 7;92(4):444-52. doi: 10.1161/01.RES.0000059415.25070.54. Epub 2003 Jan 30.
Macromolecules are transported in and out of the nucleus through nuclear pores. It is poorly understood how these megadalton conduits support nucleocytoplasmic traffic during genetic reprogramming associated with cell commitment to a specific lineage. Murine embryonic stem cells were differentiated into cardiomyocytes within embryoid bodies, and contracting cells expressing myocardial-specific proteins were isolated from the mesodermal layer. Compared with postmitotic cardiac cells from heart muscle, these proliferative and differentiating stem cell-derived cardiomyocytes demonstrated a significantly lower density of nuclear pores. At nanoscale resolution, the pore channel was commonly unoccupied in heart muscle-isolated cardiac cells, yet a dense material, presumably the central transporter, protruded toward the cytosolic face of the nuclear pore complex in stem cell-derived cardiomyocytes. Stem cell-derived cardiac cells distributed the nuclear transport factor Ran in the nucleus, decreased the number of spare nuclear pore complexes from the cytosolic annulate lamellae reservoir, and expressed a set of nucleoporins, NUP214, NUP358, NUP153, and p62, involved in nuclear transport. Stem cell-derived cardiomyocytes secured transport of nuclear constitutive proteins, cardiogenic transcription factors, and cell cycle regulators, including the prototypic histone H1, myocyte enhancer binding factor 2, and p53. Thus, differentiating stem cell-derived cardiomyocytes undergo structural adaptation and mobilize nuclear transport regulators in support of nucleocytoplasmic communication during commitment to mature cardiac lineage.
大分子通过核孔进出细胞核。在与细胞向特定谱系分化相关的基因重编程过程中，这些兆道尔顿级别的通道如何支持核质运输，目前还知之甚少。将小鼠胚胎干细胞在胚状体中分化为心肌细胞，并从中间胚层分离出表达心肌特异性蛋白的收缩细胞。与来自心肌的有丝分裂后心脏细胞相比，这些增殖和分化的干细胞来源的心肌细胞显示出核孔密度显著降低。在纳米级分辨率下，心肌分离的心脏细胞中的孔道通常是空的，但在干细胞来源的心肌细胞中，一种致密物质（可能是中央转运体）向核孔复合体的胞质面突出。干细胞来源的心脏细胞在细胞核中分布核转运因子Ran，减少胞质环层储库中备用核孔复合体的数量，并表达一组参与核运输的核孔蛋白，即NUP214、NUP358、NUP153和p62。干细胞来源的心肌细胞确保了核组成蛋白、心脏发生转录因子和细胞周期调节因子的运输，包括典型的组蛋白H1、肌细胞增强子结合因子2和p53。因此，分化中的干细胞来源的心肌细胞会进行结构适应，并调动核运输调节因子，以支持其向成熟心脏谱系分化过程中的核质通讯。
