title: Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute and Department of Stem Cell and Regenerative Biology, Harvard University and Harvard Medical School, Cambridge, Massachusetts, USA.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Polo
authors.forename: Susanna
authors.initials: S
authors.lastname: Liu
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Figueroa
authors.forename: Warakorn
authors.initials: W
authors.lastname: Kulalert
authors.forename: Sarah
authors.initials: S
authors.lastname: Eminli
authors.forename: Kah Yong
authors.initials: KY
authors.lastname: Tan
authors.forename: Effie
authors.initials: E
authors.lastname: Apostolou
authors.forename: Matthias
authors.initials: M
authors.lastname: Stadtfeld
authors.forename: Yushan
authors.initials: Y
authors.lastname: Li
authors.forename: Toshi
authors.initials: T
authors.lastname: Shioda
authors.forename: Sridaran
authors.initials: S
authors.lastname: Natesan
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Wagers
authors.forename: Ari
authors.initials: A
authors.lastname: Melnick
authors.forename: Todd
authors.initials: T
authors.lastname: Evans
authors.forename: Konrad
authors.initials: K
authors.lastname: Hochedlinger
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D057890:Epigenomics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology; D013234:Stem Cells / Q000166:cytology; D014158:Transcription, Genetic