The role of Krüppel-like factors in the reprogramming of somatic cells to induced pluripotent stem cells
Mandayam O. Nandan1 and Vincent W. Yang1,2
1Division of Digestive Diseases, Department of Medicine and 2Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia, USA.
Offprint requests to: Vincent W. Yang, MD, PhD, Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, 201 Whitehead Biomedical Research Building, 615 Michael Street, Atlanta, GA 30322, USA. e-mail: vyang@emory.edu
Summary. The potential for clinical application of pluripotent embryonic stem cells is immense but hampered by moral and ethical complications. Recent advances in the reprogramming of somatic cells by defined factors to a state that resemble embryonic stem cells have created tremendous excitement in the field. Four factors, Sox2, Oct4, Klf4 and c-Myc, when exogenously introduced into somatic cells, can lead to the formation of induced pluripotent stem (iPS) cells that have the capacity for self-renewal and differentiation into tissues of all three germ layers. In this review, we focus on the role of Krüppel-like factors (KLFs) in regulating somatic cell reprogramming. KLFs are zinc finger-containing transcription factors with diverse biological functions. We first provide an overview of the KLF family of regulatory proteins, paying special attention to the established biological and biochemical functions of KLF4 and KLF5. We then review the role of KLFs in somatic cell reprogramming and delineate the putative mechanism by which KLFs participates the establishment and self-renewal of iPS cells. Further research is likely to provide additional insight into the mechanisms of somatic cell reprogramming and refinement of the technique with which to generate clinically relevant iPS cells. Histol Histopathol 24, 1343-1355 (2009)
Key words: KLF, iPS cells, ES cells, Reprogramming, Somatic cells
DOI: 10.14670/HH-24.1343