Pluripotent Stem Cells Induced from Mouse Somatic Cells by Small-Molecule Compounds

Abstract

Pluripotent stem cells can be induced from somatic cells, providing an unlimited cell resource, with potential for studying disease and use in regenerative medicine. However, genetic manipulation and technically challenging strategies such as nuclear transfer used in reprogramming limit their clinical applications. Here, we show that pluripotent stem cells can be generated from mouse somatic cells at a frequency up to 0.2% using a combination of seven small-molecule compounds. The chemically induced pluripotent stem cells resemble embryonic stem cells in terms of their gene expression profiles, epigenetic status, and potential for differentiation and germline transmission. By using small molecules, exogenous "master genes" are dispensable for cell fate reprogramming. This chemical reprogramming strategy has potential use in generating functional desirable cell types for clinical applications.

Xist Deficiency and Disorders of X-Inactivation in Rabbit Embryonic Stem Cells Can Be Rescued by Transcription-Factor-Mediated Conversion

“…It is reasonable to speculate that rbESCs require maintenance under specific unknown culture conditions [5,6,8,10]. Small molecules are powerful tools for manipulating cell fate, improving derivation, and reprogramming efficiency [32][33][34], and for enabling the generation of mouse iPSCs from somatic cell types without gene insertion [35]. Inhibition of the MEK and GSK3b signal pathways using 2i might facilitate derivation of nonpermissive ESCs [32].…”

Induced pluripotent stem cell (iPSCs) and their application in immunotherapy

“…9 Recently, Hou et al transformed mouse somatic cells to the pluripotent state using only small-molecule compounds, providing another convenient pathway to generate iPSCs without genetic intervention. 10 Encouragingly, Israeli scientists 11 uncovered the crucial molecular hurdle in the reprogramming process-Mbd3, a core member of the Mbd3/nucleosome remodeling and deacetylation repressor. By applying OSKM transduction plus Mbd3 depletion, they synchronically reprogrammed mouse/human somatic cells with efficiencies near 100% within 7 days, a giant leap forward in reprogramming.…”

“…24,45 In order to completely eliminate such potential hazards when using iPSC in regenerative medicine, it is exigent and imperative for us to develop safer and more convenient approaches to producing iPSCs with less immunogenicity, such as using small-molecule compounds without artificial genetic manipulation. 10 On the other hand, perhaps launching an iPSC bank containing cells from many individuals in a population for increased chances of HLA-type matching 46,47 is a more practical pathway for using iPSCs in the clinic, similar to what Yamanaka has proposed 48,49 and what has already been set up for ESCs. 50 Such a bank may save time normally spent on inducing and evaluating iPSCs created from each specific individual.…”

Direct reprogramming of somatic cells: an update

“…How the small molecules can reprogram the cell fate is a question that needs to be answered. In some cases, small molecules activate some pluripotency genes (Hou et al, 2013) as well as transcription factors (Yuan et al, 2013).…”