Cellular reprogramming consists of the conversion of differentiated cells into 
pluripotent cells; the so-called induced Pluripotent Stem Cells. iPSC are 
amenable to in vitro manipulation and, in theory, direct production of any 
differentiated cell type. Furthermore, iPSC can be obtained from sick 
individuals and subsequently used for disease modeling, drug discovery and 
regenerative treatments. iPSC production was first achieved by transducing, with 
the use of retroviral vectors, four specific transcription factors: Oct4, Klf4, 
Sox2 and c-Myc (OKSM), into primary cells in culture Takahashi and Yamanaka, 
(Cell 126(4):663-676, 2006). Many alternative protocols have since been 
proposed: repeated transfections of expression plasmids containing the four 
pluripotency-associated genes Okita et al. (Science 322(5903):949-953, 2008), 
lentiviral delivery of the four factors Sommer et al. (Stem Cells 27(3):543-549, 
2009), Sendai virus delivery Fusaki et al. (Proceedings of the Japan Academy. 
Series B, Physical and Biological Sciences 85(8):348-362, 2009), removal of the 
reprogramming vectors by 'piggyBac' transposition Woltjen et al. (Nature 
458(7239):766-770, 2009); Kaji et al. (Nature 458(7239):771-775, 2009), 
Cre-recombinase excisable viruses Soldner et al. (Cell 136(5):964-977, 2009), 
episomal vectors Yu et al. (Science 324(5928):797-801, 2009), cell-penetrating 
reprogramming proteins Zhou et al. (Stem Cells 4(5):381-384, 2009), mammalian 
artificial chromosomes Hiratsuka et al. (PLoS One 6(10):e25961, 2011) 
synthetically modified mRNAs Warren et al. (Scientific Reports 2:657, 2012), 
miRNA Anokye-Danso et al. (Cell Stem Cell 8(4):376-388, 2009); however, although 
some of these methods are commercially available, in general they still need to 
attain the reproducibility and reprogramming efficiency required for routine 
applications Mochiduki and Okita (Biotechnol Journal 7(6):789-797, 2012). Herein 
we explain, in four detailed protocols, the isolation of mouse and human somatic 
cells and their reprogramming into iPSC. All-encompassing instructions, not 
previously published in a single document, are provided for mouse and human iPSC 
colony isolation and derivation. Although mouse and human iPSC share 
similarities in the cellular reprogramming process and culture, both cell types 
need to be handled differently.