Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells

• Published in: Nature biotechnology Vol. 28; no. 8; pp. 848 - 855
• Main Authors: Wagers, Amy J, Eminli, Sarah, Evans, Todd, Liu, Susanna, Kulalert, Warakorn, Li, Yushan, Apostolou, Effie, Tan, Kah Yong, Natesan, Sridaran, Melnick, Ari, Polo, Jose M, Shioda, Toshi, Hochedlinger, Konrad, Stadtfeld, Matthias, Figueroa, Maria Eugenia
• Format: Journal Article
• Language: English
• Published: New York, NY Nature Publishing Group 01.08.2010
• Subjects: Analysis; Animals; B cells; B-Lymphocytes - cytology; Biological and medical sciences; Biotechnology; Cell Differentiation; Cell Lineage; Cells, Cultured; Diseases; Embryoid Bodies - cytology; Embryoid Bodies - metabolism; Epigenetic inheritance; Epigenomics; Fibroblasts - cytology; Fibroblasts - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Genes; Health. Pharmaceutical industry; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; Industrial applications and implications. Economical aspects; Mice; Miscellaneous; Molecular biology; Muscle, Skeletal - cytology; Polo; Rodents; Stem cells; Stem Cells - cytology; Transcription, Genetic; Origin; Transcription; Rodentia; Induced pluripotent stem cell; Somatic cell; Cell differentiation; Gene expression; In vitro; Vertebrata; Mammalia; Mouse; Epigenetics; Methylation
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt.1667

Induced pluripotent stem cells (iPSCs) have been derived from various somatic cell populations through ectopic expression of defined factors. It remains unclear whether iPSCs generated from different cell types are molecularly and functionally similar. Here we show that iPSCs obtained from mouse fibroblasts, hematopoietic and myogenic cells exhibit distinct transcriptional and epigenetic patterns. Moreover, we demonstrate that cellular origin influences the in vitro differentiation potentials of iPSCs into embryoid bodies and different hematopoietic cell types. Notably, continuous passaging of iPSCs largely attenuates these differences. Our results suggest that early-passage iPSCs retain a transient epigenetic memory of their somatic cells of origin, which manifests as differential gene expression and altered differentiation capacity. These observations may influence ongoing attempts to use iPSCs for disease modeling and could also be exploited in potential therapeutic applications to enhance differentiation into desired cell lineages.