Hartman Institute for Therapeutic Organ Regeneration

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

TitleCell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells.
Publication TypeJournal Article
Year of Publication2010
AuthorsPolo JM, Liu S, Figueroa MEugenia, Kulalert W, Eminli S, Tan KYong, Apostolou E, Stadtfeld M, Li Y, Shioda T, Natesan S, Wagers AJ, Melnick A, Evans T, Hochedlinger K
JournalNat Biotechnol
Volume28
Issue8
Pagination848-55
Date Published2010 Aug
ISSN1546-1696
KeywordsAnimals, B-Lymphocytes, Cell Differentiation, Cell Lineage, Cells, Cultured, Embryoid Bodies, Epigenomics, Fibroblasts, Gene Expression Profiling, Hematopoietic Stem Cells, Induced Pluripotent Stem Cells, Mice, Muscle, Skeletal, Stem Cells, Transcription, Genetic
Abstract

<p>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.</p>

DOI10.1038/nbt.1667
Alternate JournalNat Biotechnol
PubMed ID20644536
PubMed Central IDPMC3148605
Grant List / HHMI / Howard Hughes Medical Institute / United States
R01 HL056182 / HL / NHLBI NIH HHS / United States
P30 DK036836 / DK / NIDDK NIH HHS / United States
DP2 OD004345 / OD / NIH HHS / United States
HL056182 / HL / NHLBI NIH HHS / United States
R37 HL056182 / HL / NHLBI NIH HHS / United States
R01 HD058013 / HD / NICHD NIH HHS / United States
R37 HL056182-15 / HL / NHLBI NIH HHS / United States
P30DK036836 / DK / NIDDK NIH HHS / United States
DP2 OD004345-01 / OD / NIH HHS / United States

Weill Cornell Medicine
Hartman Institute for Therapeutic Organ Regeneration
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