Bacteria to form induced pluripotent stem cells

Abstract In 2006, Takahashi and Yamanaka reported the generation of mouse and human induced pluripotent stem cells (iPS cells) by retroviral gene transduction of four transcription factors, famously known as Yamanaka factors (OCT4, SOX2, Klf4, and c-Myc) (Takahashi et al., 2007; Takahashi and Yamanaka, 2006). iPS cells show stemness properties (self-renewal and differentiation into three germ layers derivatives) that are comparable to the embryonic stem cells (ES cells). However, conventional iPS cells technique is not entirely safe because of its procedural difficulties, lower efficiency, and the risk of cancer formation (Luo et al., 2013; Rais et al., 2013). Meanwhile, several bacteria-mediated strategies have been identified that can reprogram differentiated cells into stem cell–like state and dedifferentiate into three germ layer derived cells. In 2012, Fuji et al. reported Helicobacter pylori bacteria can reprogram gastric epithelial cells into intestinal stem/progenitor-like cells in vivo by inducing homeobox transcription factors (CDX) during intestinal metaplasia (Fujii et al., 2012). In the same year, our group discovered that lactic acid bacteria (LAB) can reprogram human dermal fibroblast (HDF) into stem cell–like cells in vitro that can differentiate into all three germ layer derivatives (Ohta et al., 2012). Later, Masaki et al. reported that leprosy-causing bacterium Mycobacterium leprae reprograms adult Schwann cells into stem cell–like cells in vivo that differentiate into mesenchymal, skeletal, and smooth muscle cells facilitating infection dissemination (Masaki et al., 2013). In 2017, Ikeda et al. reported that Wolbachia pipientis bacterial proteins can accelerate traditional retroviral-mediated iPS cells generation process (Ikeda et al., 2017). All these studies substantiate the epigenetic potentials of bacteria or its material to induce stemness in differentiated cells. Such microbial potentials might be connected with the endosymbiotic theory, which states that eukaryotic cells are generated through endosymbiotic relationship between prokaryotes (Woese et al., 1990). In this chapter, we briefly discussed about several evidences of bacterial impact on cellular homeostasis and plasticity. We largely focused on LAB-mediated cell reprogramming of HDF cells as a potential technique for future iPS cells generation.