The quantitative proteomes of human‐induced pluripotent stem cells and embryonic stem cells

• Published in: Molecular systems biology 2011-11, Vol.7 (1), p.550-n/a
• Main Authors: Munoz, Javier, Low, Teck Y, Kok, Yee J, Chin, Angela, Frese, Christian K, Ding, Vanessa, Choo, Andre, Heck, Albert J R
• Format: Article
• Language: English
• Subjects: Abundance; Adhesion; Analogies; Animal models; Antigen processing; Antigens; Biotechnology; Cation exchange; Cell adhesion; Cell Line; Cell lines; Complementation; Differentiation; Electron transfer; EMBO31; Embryo cells; Embryo fibroblasts; Embryonic Stem Cells - cytology; Embryonic Stem Cells - metabolism; Embryos; Energy of dissociation; Ethical standards; Experiments; Fibroblasts; Fractionation; Gene expression; Gene Expression Profiling - methods; Gene regulation; Genomes; Hip; human embryonic stem cells; Humans; human‐induced pluripotent stem cells; Mass Spectrometry; Mass spectroscopy; Metabolism; Molecular chains; Oligonucleotide Array Sequence Analysis; Organic chemistry; Peptides; Pluripotency; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - metabolism; Precursors; Proteins; Proteome - analysis; Proteome - genetics; Proteome - metabolism; Proteomics; quantitation; Similarity; Somatic cells; Stem cell transplantation; Stem cells; Studies; Transcription
• ISSN: 1744-4292; 1744-4292
• DOI: 10.1038/msb.2011.84

Assessing relevant molecular differences between human‐induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) is important, given that such differences may impact their potential therapeutic use. Controversy surrounds recent gene expression studies comparing hiPSCs and hESCs. Here, we present an in‐depth quantitative mass spectrometry‐based analysis of hESCs, two different hiPSCs and their precursor fibroblast cell lines. Our comparisons confirmed the high similarity of hESCs and hiPSCS at the proteome level as 97.8% of the proteins were found unchanged. Nevertheless, a small group of 58 proteins, mainly related to metabolism, antigen processing and cell adhesion, was found significantly differentially expressed between hiPSCs and hESCs. A comparison of the regulated proteins with previously published transcriptomic studies showed a low overlap, highlighting the emerging notion that differences between both pluripotent cell lines rather reflect experimental conditions than a recurrent molecular signature. An in‐depth proteomic comparison of human‐induced pluripotent stem cells, and their parent fibroblast cells, with embryonic stem cells shows that the reprogramming process comprehensively remodels protein expression levels, creating cells that closely resemble natural stem cells. Synopsis An in‐depth proteomic comparison of human‐induced pluripotent stem cells, and their parent fibroblast cells, with embryonic stem cells shows that the reprogramming process comprehensively remodels protein expression levels, creating cells that closely resemble natural stem cells. Human embryonic stem cells (hESCs) are capable of self‐renewal and multi‐lineage differentiation. However, the use of hESCs for clinical treatment entails ethical issues as they are derived from human embryos. Recently, reprogramming of somatic cells to an embryonic stem cell‐like state, named induced pluripotent stem cells (iPSCs), was achieved through ectopic expression of defined factors. In addition to their clinical potential, hiPSCs represent a unique tool to develop cellular models for human diseases as well. Although current functional assays (e.g., tetraploid complementation) have confirmed the pluripotency of hiPSCs, there might still be significant differences (e.g., differentiation potential) when compared with their natural hESCs counterparts. Consequently, an extensive molecular characterization to address differences and similarities between these two pluri