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Title: Transcription factor KLF7 regulates differentiation of neuroectodermal and mesodermal cell lineages

Abstract

Previous gene targeting studies in mice have implicated the nuclear protein Krueppel-like factor 7 (KLF7) in nervous system development while cell culture assays have documented its involvement in cell cycle regulation. By employing short hairpin RNA (shRNA)-mediated gene silencing, here we demonstrate that murine Klf7 gene expression is required for in vitro differentiation of neuroectodermal and mesodermal cells. Specifically, we show a correlation of Klf7 silencing with down-regulation of the neuronal marker microtubule-associated protein 2 (Map2) and the nerve growth factor (NGF) tyrosine kinase receptor A (TrkA) using the PC12 neuronal cell line. Similarly, KLF7 inactivation in Klf7-null mice decreases the expression of the neurogenic marker brain lipid-binding protein/fatty acid-binding protein 7 (BLBP/FABP7) in neural stem cells (NSCs). We also report that Klf7 silencing is detrimental to neuronal and cardiomyocytic differentiation of embryonic stem cells (ESCs), in addition to altering the adipogenic and osteogenic potential of mouse embryonic fibroblasts (MEFs). Finally, our results suggest that genes that are key for self-renewal of undifferentiated ESCs repress Klf7 expression in ESCs. Together with previous findings, these results provide evidence that KLF7 has a broad spectrum of regulatory functions, which reflect the discrete cellular and molecular contexts in which this transcription factor operates.

Authors:
 [1];  [2];  [1];  [2];  [3];  [3];  [4];  [5];  [1]
  1. Institute of Genetics and Biophysics 'A. Buzzati-Traverso,' CNR, 80131 Naples (Italy)
  2. (Italy)
  3. CEINGE Biotecnologie Avanzate, 80145 Naples (Italy)
  4. Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4 (Canada)
  5. Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029 (United States)
Publication Date:
OSTI Identifier:
22209896
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 316; Journal Issue: 14; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BRAIN; CATTLE; CELL CULTURES; CELL CYCLE; FIBROBLASTS; GROWTH FACTORS; HORSES; IN VITRO; MICE; MICROTUBULES; PHOSPHATES; POLYMERASE CHAIN REACTION; RECEPTORS; RNA; STEM CELLS; TRANSCRIPTION FACTORS; TYROSINE

Citation Formats

Caiazzo, Massimiliano, E-mail: caiazzo@igb.cnr.it, Istituto di diagnosi e cura 'Hermitage Capodimonte,' 80131 Naples, Colucci-D'Amato, Luca, E-mail: luca.colucci@unina2.it, Dipartimento di Scienze della Vita, Seconda Universita di Napoli, 81100 Caserta, Esposito, Maria T., E-mail: maria_teresa.esposito@kcl.ac.uk, Parisi, Silvia, E-mail: parisi@ceinge.unina.it, Stifani, Stefano, E-mail: stefano.stifani@mcgill.ca, Ramirez, Francesco, E-mail: francesco.ramirez@mssm.edu, and Porzio, Umberto di, E-mail: diporzio@igb.cnr.it. Transcription factor KLF7 regulates differentiation of neuroectodermal and mesodermal cell lineages. United States: N. p., 2010. Web. doi:10.1016/J.YEXCR.2010.05.021.
Caiazzo, Massimiliano, E-mail: caiazzo@igb.cnr.it, Istituto di diagnosi e cura 'Hermitage Capodimonte,' 80131 Naples, Colucci-D'Amato, Luca, E-mail: luca.colucci@unina2.it, Dipartimento di Scienze della Vita, Seconda Universita di Napoli, 81100 Caserta, Esposito, Maria T., E-mail: maria_teresa.esposito@kcl.ac.uk, Parisi, Silvia, E-mail: parisi@ceinge.unina.it, Stifani, Stefano, E-mail: stefano.stifani@mcgill.ca, Ramirez, Francesco, E-mail: francesco.ramirez@mssm.edu, & Porzio, Umberto di, E-mail: diporzio@igb.cnr.it. Transcription factor KLF7 regulates differentiation of neuroectodermal and mesodermal cell lineages. United States. doi:10.1016/J.YEXCR.2010.05.021.
Caiazzo, Massimiliano, E-mail: caiazzo@igb.cnr.it, Istituto di diagnosi e cura 'Hermitage Capodimonte,' 80131 Naples, Colucci-D'Amato, Luca, E-mail: luca.colucci@unina2.it, Dipartimento di Scienze della Vita, Seconda Universita di Napoli, 81100 Caserta, Esposito, Maria T., E-mail: maria_teresa.esposito@kcl.ac.uk, Parisi, Silvia, E-mail: parisi@ceinge.unina.it, Stifani, Stefano, E-mail: stefano.stifani@mcgill.ca, Ramirez, Francesco, E-mail: francesco.ramirez@mssm.edu, and Porzio, Umberto di, E-mail: diporzio@igb.cnr.it. 2010. "Transcription factor KLF7 regulates differentiation of neuroectodermal and mesodermal cell lineages". United States. doi:10.1016/J.YEXCR.2010.05.021.
@article{osti_22209896,
title = {Transcription factor KLF7 regulates differentiation of neuroectodermal and mesodermal cell lineages},
author = {Caiazzo, Massimiliano, E-mail: caiazzo@igb.cnr.it and Istituto di diagnosi e cura 'Hermitage Capodimonte,' 80131 Naples and Colucci-D'Amato, Luca, E-mail: luca.colucci@unina2.it and Dipartimento di Scienze della Vita, Seconda Universita di Napoli, 81100 Caserta and Esposito, Maria T., E-mail: maria_teresa.esposito@kcl.ac.uk and Parisi, Silvia, E-mail: parisi@ceinge.unina.it and Stifani, Stefano, E-mail: stefano.stifani@mcgill.ca and Ramirez, Francesco, E-mail: francesco.ramirez@mssm.edu and Porzio, Umberto di, E-mail: diporzio@igb.cnr.it},
abstractNote = {Previous gene targeting studies in mice have implicated the nuclear protein Krueppel-like factor 7 (KLF7) in nervous system development while cell culture assays have documented its involvement in cell cycle regulation. By employing short hairpin RNA (shRNA)-mediated gene silencing, here we demonstrate that murine Klf7 gene expression is required for in vitro differentiation of neuroectodermal and mesodermal cells. Specifically, we show a correlation of Klf7 silencing with down-regulation of the neuronal marker microtubule-associated protein 2 (Map2) and the nerve growth factor (NGF) tyrosine kinase receptor A (TrkA) using the PC12 neuronal cell line. Similarly, KLF7 inactivation in Klf7-null mice decreases the expression of the neurogenic marker brain lipid-binding protein/fatty acid-binding protein 7 (BLBP/FABP7) in neural stem cells (NSCs). We also report that Klf7 silencing is detrimental to neuronal and cardiomyocytic differentiation of embryonic stem cells (ESCs), in addition to altering the adipogenic and osteogenic potential of mouse embryonic fibroblasts (MEFs). Finally, our results suggest that genes that are key for self-renewal of undifferentiated ESCs repress Klf7 expression in ESCs. Together with previous findings, these results provide evidence that KLF7 has a broad spectrum of regulatory functions, which reflect the discrete cellular and molecular contexts in which this transcription factor operates.},
doi = {10.1016/J.YEXCR.2010.05.021},
journal = {Experimental Cell Research},
number = 14,
volume = 316,
place = {United States},
year = 2010,
month = 8
}
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