scholarly journals In Vitro Cytotoxicity of Nanoparticles in Mammalian Germ-Line Stem Cell

2005 ◽  
Vol 88 (2) ◽  
pp. 285-286 ◽  
Author(s):  
Maria Pilar Vinardell
2020 ◽  
Vol 117 (7) ◽  
pp. 3603-3609 ◽  
Author(s):  
Fan Zou ◽  
Renjun Tu ◽  
Bo Duan ◽  
Zhenlin Yang ◽  
Zhaohua Ping ◽  
...  

5-Methylcytosine (m5C) is a RNA modification that exists in tRNAs and rRNAs and was recently found in mRNAs. Although it has been suggested to regulate diverse biological functions, whether m5C RNA modification influences adult stem cell development remains undetermined. In this study, we show that Ypsilon schachtel (YPS), a homolog of human Y box binding protein 1 (YBX1), promotes germ line stem cell (GSC) maintenance, proliferation, and differentiation in the Drosophila ovary by preferentially binding to m5C-containing RNAs. YPS is genetically demonstrated to function intrinsically for GSC maintenance, proliferation, and progeny differentiation in the Drosophila ovary, and human YBX1 can functionally replace YPS to support normal GSC development. Highly conserved cold-shock domains (CSDs) of YPS and YBX1 preferentially bind to m5C RNA in vitro. Moreover, YPS also preferentially binds to m5C-containing RNAs, including mRNAs, in germ cells. The crystal structure of the YBX1 CSD-RNA complex reveals that both hydrophobic stacking and hydrogen bonds are critical for m5C binding. Overexpression of RNA-binding–defective YPS and YBX1 proteins disrupts GSC development. Taken together, our findings show that m5C RNA modification plays an important role in adult stem cell development.


Genetics ◽  
2004 ◽  
Vol 167 (2) ◽  
pp. 707-723 ◽  
Author(s):  
Cordula Schulz ◽  
Amy A. Kiger ◽  
Salli I. Tazuke ◽  
Yukiko M. Yamashita ◽  
Luiz C. Pantalena-Filho ◽  
...  

1999 ◽  
Vol 19 (4) ◽  
pp. 2635-2643 ◽  
Author(s):  
A. Brehm ◽  
K. Ohbo ◽  
W. Zwerschke ◽  
V. Botquin ◽  
P. Jansen-Dürr ◽  
...  

ABSTRACT Activation of transcription by Oct-4 from remote binding sites requires a cofactor that is restricted to embryonal stem cells. The adenovirus E1A protein can mimic the activity of this stem cell-specific factor and stimulates Oct-4 activity in differentiated cells. Here we characterize the Oct-4–E1A interaction and show that the E1A 289R protein harbors two independent Oct-4 binding sites, both of which specifically interact with the POU domain of Oct-4. Furthermore, we demonstrate that, like E1A, the human papillomavirus E7 oncoprotein also specifically binds to the Oct-4 POU domain. E7 and Oct-4 can form a complex both in vitro and in vivo. Expression of E7 in differentiated cells stimulates Oct-4-mediated transactivation from distal binding sites. Moreover, Oct-4, but not other Oct factors, is active when expressed in cells transformed by human papillomavirus. Our results suggest that different viruses have evolved oncoproteins that share the ability to target Oct-4 and to mimic a stem cell-specific activity.


1998 ◽  
Vol 5 (1) ◽  
pp. 54A-54A
Author(s):  
S TAZUKE ◽  
C SCHULZ ◽  
M FOGARTY ◽  
A GUICHET ◽  
A EPHRUSSI ◽  
...  

2014 ◽  
Vol 20 (3) ◽  
pp. 330-340 ◽  
Author(s):  
Kimberley J. Lewis ◽  
Nicole C. Silvester ◽  
Steven Barberini-Jammaers ◽  
Sammy A. Mason ◽  
Sarah A. Marsh ◽  
...  

The emergence of human stem cell–derived cardiomyocyte (hSCCM)–based assays in the cardiovascular (CV) drug discovery sphere requires the development of improved systems for interrogating the rich information that these cell models have the potential to yield. We developed a new analytical framework termed SALVO (synchronization, amplitude, length, and variability of oscillation) to profile the amplitude and temporal patterning of intra- and intercellular calcium signals in hSCCM. SALVO quantified drug-induced perturbations in the calcium signaling “fingerprint” in spontaneously contractile hSCCM. Multiparametric SALVO outputs were integrated into a single index of in vitro cytotoxicity that confirmed the rank order of perturbation as astemizole > thioridazine > cisapride > flecainide > valdecoxib > sotalol > nadolol ≈ control. This rank order of drug-induced Ca2+ signal disruption is in close agreement with the known arrhythmogenic liabilities of these compounds in humans. Validation of the system using a second set of compounds and hierarchical cluster analysis demonstrated the utility of SALVO to discriminate drugs based on their mechanisms of action. We discuss the utility of this new mechanistically agnostic system for the evaluation of in vitro drug cytotoxicity in hSCCM syncytia and the potential placement of SALVO in the early stage drug screening framework.


2003 ◽  
Vol 68 (1) ◽  
pp. 167-173 ◽  
Author(s):  
Mito Kanatsu-Shinohara ◽  
Narumi Ogonuki ◽  
Kimiko Inoue ◽  
Atsuo Ogura ◽  
Shinya Toyokuni ◽  
...  

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