Transcription factors (TFs) are key actors of the control of gene expression and consequently of every major process within cells, ranging from cell fate determination, cell cycle control and response to environment. Their ectopic expression has proven high potential in reprogramming cells for regenerative medicine; ontogenesis studies and cell based modelling. Direct delivery of proteins could represent an alternative to current reprogramming methods using gene transfer but still needs technological improvements. Herein, we set-up an efficient cellular penetration of recombinant TFs fused to the minimal transduction domain (MD) from the ZEBRA protein. We show that ZEBRA MD-fused TFs applied on primary human fibroblasts and cord blood CD34 hematopoietic stem cells route through the cytoplasm to the nucleus. The delivery of Oct4, Sox2 and Nanog by MD leads to the activation of mRNA transcripts from genes regulated by these TFs. Moreover, the expression of genes involved in the pluripotency network but not directly bound by these TFs, is also induced. Overall, the repeated application of MD-Oct4, MD-Sox2, MD-Nanog TFs and the post-transcriptional regulator RNA-binding protein MD-Lin28a, triggers the rejuvenation of human fibroblasts and CD34 cells. This study provides powerful tools for cell fate reprogramming without genetic interferences.
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http://dx.doi.org/10.1016/j.ijpharm.2017.06.073 | DOI Listing |
PLoS One
December 2024
Unidad de Investigación, Hospital Universitario de Canarias, Instituto de Investigación Sanitaria de Canarias (IISC), La Laguna, Tenerife, Spain.
Spinocerebellar ataxia type 3 (SCA3) is a cureless neurodegenerative disease recognized as the most prevalent form of dominantly inherited ataxia worldwide. The main hallmark of SCA3 is the expansion of a polyglutamine tract located in the C-terminal of Ataxin-3 (or ATXN3) protein, that triggers the mis-localization and toxic aggregation of ATXN3 in neuronal cells. The propensity of wild type and polyglutamine-expanded ATXN3 proteins to aggregate has been extensively studied over the last decades.
View Article and Find Full Text PDFMol Plant Pathol
December 2024
Plant Molecular and Cell Biology Program, University of Florida, Gainesville, Florida, USA.
Viroids are single-stranded circular noncoding RNAs that mainly infect crops. Upon infection, nuclear-replicating viroids engage host DNA-dependent RNA polymerase II for RNA-templated transcription, which is facilitated by a host protein TFIIIA-7ZF. The sense-strand and minus-strand RNA intermediates are differentially localised to the nucleolus and nucleoplasm regions, respectively.
View Article and Find Full Text PDFElife
December 2024
Howard Hughes Medical Institute, Stanford University, Stanford, United States.
Defining the cellular factors that drive growth rate and proteome composition is essential for understanding and manipulating cellular systems. In bacteria, ribosome concentration is known to be a constraining factor of cell growth rate, while gene concentration is usually assumed not to be limiting. Here, using single-molecule tracking, quantitative single-cell microscopy, and modeling, we show that genome dilution in cells arrested for DNA replication limits total RNA polymerase activity within physiological cell sizes across tested nutrient conditions.
View Article and Find Full Text PDFParasitol Res
December 2024
Institute of Hygiene and Microbiology, University of Würzburg, Josef-Schneider-Strasse 2, 97080, Würzburg, Germany.
Pluripotent somatic stem cells are the drivers of unlimited growth of Echinococcus multilocularis metacestode tissue within the organs of the intermediate host. To understand the dynamics of parasite proliferation within the host, it is therefore important to delineate basic mechanisms of Echinococcus stem cell maintenance and differentiation. We herein undertake the first step towards characterizing the role of an evolutionarily old metazoan cell-cell communication system, delta/notch signalling, in Echinococcus cell fate decisions.
View Article and Find Full Text PDFPlanta
December 2024
Federal Scientific Center of the East Asia Terrestrial Biodiversity of the Russian Academy of Sciences Far Eastern Branch, FGBUN FNC Bioraznoobrazia Nazemnoj Bioty Vostocnoj Azii Dal'nevostocnogo Otdelenia Rossijskoj Akademii Nauk, Vladivostok, 690022, Russia.
Long-term cultured calli may experience a biosynthetic shift due to the IAA-dependent expression of the rolA gene, which also affects ROS metabolism. The "hairy root" syndrome is caused by the root-inducing Ri-plasmid of Rhizobium rhizogenes, also known as Agrobacterium rhizogenes. The Ri-plasmid contains genes known as rol genes or root oncogenic loci, which promote root development.
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