scholarly journals Ethanol Inactivated Mouse Embryonic Fibroblasts Maintain the Self-Renew and Proliferation of Human Embryonic Stem Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0130332 ◽  
Author(s):  
Boxian Huang ◽  
Song Ning ◽  
Lili Zhuang ◽  
Chunyan Jiang ◽  
Yugui Cui ◽  
...  
Blood ◽  
2005 ◽  
Vol 105 (12) ◽  
pp. 4598-4603 ◽  
Author(s):  
Lisheng Wang ◽  
Li Li ◽  
Pablo Menendez ◽  
Chantal Cerdan ◽  
Mickie Bhatia

Abstract To date, hematopoietic development of human embryonic stem cells (hESCs) has been limited to cell lines cultured in the presence of either mouse embryonic fibroblasts (MEFs) or MEF-conditioned media (MEF-CM). Anonymous xenogenic factors from MEFs or MEF-CM complicate studies of hESC self-renewal and also raise concerns for the potential clinical applications of generating primitive hematopoietic cells from hESC lines maintained under these ambiguous conditions. Here, we demonstrate that hESCs can be cultured over 30 passages in defined conditions in the absence of MEFs or MEF-CM using only serum replacement (SR) media and high concentrations of basic fibroblast growth factor (SR-bFGF). Similar to hESCs cultured in MEF-CM, hESCs cultured in SR-bFGF sustained characteristics of undifferentiated hESCs, proliferative potential, normal karyotype, in vitro and in vivo 3 germ-layer specification and gave rise to hemogenic-endothelial precursors required for subsequent primitive hematopoietic development. Our report demonstrates that anonymous factors produced by feeder cells are not necessary for hESC maintenance and subsequent hematopoietic specification, thereby providing a defined system for studies of hESC self-renewal and hESC-derived hematopoiesis. (Blood. 2005;105:4598-4603)


2009 ◽  
Vol 30 (5) ◽  
pp. 1171-1181 ◽  
Author(s):  
Gordin Zupkovitz ◽  
Reinhard Grausenburger ◽  
Reinhard Brunmeir ◽  
Silvia Senese ◽  
Julia Tischler ◽  
...  

ABSTRACT Histone deacetylases (HDACs) are chromatin-modifying enzymes that are involved in the regulation of proliferation, differentiation and development. HDAC inhibitors induce cell cycle arrest, differentiation, or apoptosis in tumor cells and are therefore promising antitumor agents. Numerous genes were found to be deregulated upon HDAC inhibitor treatment; however, the relevant target enzymes are still unidentified. HDAC1 is required for mouse development and unrestricted proliferation of embryonic stem cells. We show here that HDAC1 reversibly regulates cellular proliferation and represses the cyclin-dependent kinase inhibitor p21 in embryonic stem cells. Disruption of the p21 gene rescues the proliferation phenotype of HDAC1−/− embryonic stem cells but not the embryonic lethality of HDAC1−/− mice. In the absence of HDAC1, mouse embryonic fibroblasts scarcely undergo spontaneous immortalization and display increased p21 expression. Chromatin immunoprecipitation assays demonstrate a direct regulation of the p21 gene by HDAC1 in mouse embryonic fibroblasts. Transformation with simian virus 40 large T antigen or ablation of p21 restores normal immortalization of primary HDAC1−/− fibroblasts. Our data demonstrate that repression of the p21 gene is crucial for HDAC1-mediated control of proliferation and immortalization. HDAC1 might therefore be one of the relevant targets for HDAC inhibitors as anticancer drugs.


Cell Cycle ◽  
2016 ◽  
Vol 15 (21) ◽  
pp. 2931-2942 ◽  
Author(s):  
Areta M. Czerwinska ◽  
Joanna Nowacka ◽  
Magdalena Aszer ◽  
Sylwia Gawrzak ◽  
Karolina Archacka ◽  
...  

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