Stem cells transform into a cardiac phenotype with remodeling of the nuclear transport machinery

被引：45

作者：

Perez-Terzic C. ^{[1
]}

Faustino R.S. ^{[2
]}

Boorsma B.J. ^{[2
]}

Arrell D.K. ^{[2
]}

Niederländer N.J. ^{[2
]}

Behfar A. ^{[2
]}

Terzic A. ^{[2
]}

机构：

[1] Department of Physical Medicine and Rehabilitation, Cardiovascular Rehabilitation, Mayo Clinic College of Medicine, Rochester, MN

[2] Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN

来源：

Nature Clinical Practice Cardiovascular Medicine | 2007年 / 4卷 / Suppl 1期

关键词：

D O I：

10.1038/ncpcardio0763

中图分类号：

学科分类号：

摘要：

Nuclear transport of transcription factors is a critical step in stem cell commitment to a tissue-specific lineage. While it is recognized that nuclear pores are gatekeepers of nucleocytoplasmic exchange, it is unknown how the nuclear transport machinery becomes competent to support genetic reprogramming and cell differentiation. Here, we report the dynamics of nuclear transport factor expression and nuclear pore microanatomy during cardiac differentiation of embryonic stem cells. Cardiac progeny derived from pluripotent stem cells displayed a distinct proteomic profile characterized by the emergence of cardiac-specific proteins. This profile correlated with the nuclear translocation of cardiac transcription factors. The nuclear transport genes, including nucleoporins, importins, exportins, transportins, and Ran-related factors, were globally downregulated at the genomic level, streamlining the differentiation program underlying stem cell-derived cardiogenesis. Establishment of the cardiac molecular phenotype was associated with an increased density of nuclear pores spanning the nuclear envelope. At nanoscale resolution, individual nuclear pores exhibited conformational changes resulting in the expansion of the pore diameter and an augmented probability of conduit occupancy. Thus, embryonic stem cells undergo adaptive remodeling of the nuclear transport infrastructure associated with nuclear translocation of cardiac transcription factors and execution of the cardiogenic program, underscoring the plasticity of the nucleocytoplasmic trafficking machinery in accommodating differentiation requirements.

引用

页码：S68 / S76

页数：8

共 37 条

[1] Wente S.R., Gatekeepers of the nucleus, Science, 288, pp. 1374-1377, (2000)
[2] Weis K., Regulating access to the genome: Nucleocytoplasmic transport throughout the cell cycle, Cell, 112, pp. 441-451, (2003)
[3] Smith A.E., Et al., Systems analysis of Ran transport, Science, 295, pp. 488-491, (2002)
[4] Dzeja P.P., Et al., Energetic communication between mitochondria and nucleus directed by catalyzed phosphotransfer, Proc Nat Acad Sci USA, 99, pp. 10156-10161, (2002)
[5] Behfar A., Et al., Stem cell differentiation requires a paracrine pathway in the heart, FASEB J, 16, pp. 1558-1566, (2002)
[6] Perez-Terzic C., Et al., Structural adaptation of the nuclear pore complex in stem cell-derived cardiomyocytes, Circ Res, 92, pp. 444-452, (2003)
[7] Perez-Terzic C., Et al., Directed inhibition of nuclear import in cellular hypertrophy, J Biol Chem, 276, pp. 20566-20571, (2001)
[8] Shevchenko A., Et al., Mass spectrometric sequencing of proteins from silver-stained polyacrylamide gels, Anal Chem, 68, pp. 850-858, (1996)
[9] Perkins D.N., Et al., Probability-based protein identification by searching sequence databases using mass spectrometry data, Electrophoresis, 20, pp. 3551-3567, (1999)
[10] Livak K.J., Schmittgen T.D., Analysis of relative gene expression data using real-time quantitative PCR and the 2<sup>-ΔΔC</sup><sub>T</sub> method, Methods, 25, pp. 402-408, (2001)

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