Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells.
The reprogramming of somatic cells into induced pluripotent stem (iPS) cells upon overexpression of the transcription factors Oct4, Sox2, Klf4 and cMyc is inefficient. It has been assumed that the somatic differentiation state provides a barrier for efficient reprogramming; however, direct evidence for this notion is lacking. Here, we tested the potential of mouse hematopoietic cells at different stages of differentiation to be reprogrammed into iPS cells. We show that hematopoietic stem and progenitor cells give rise to iPS cells up to 300 times more efficiently than terminally differentiated B and T cells do, yielding reprogramming efficiencies of up to 28%. Our data provide evidence that the differentiation stage of the starting cell has a critical influence on the efficiency of reprogramming into iPS cells. Moreover, we identify hematopoietic progenitors as an attractive cell type for applications of iPS cell technology in research and therapy.
Eminli
Sarah
S
Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Boston, Massachusetts, USA.
Foudi
Adlen
A
Stadtfeld
Matthias
M
Maherali
Nimet
N
Ahfeldt
Tim
T
Mostoslavsky
Gustavo
G
Hock
Hanno
H
Hochedlinger
Konrad
K
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D002678:Chimera; D005347:Fibroblasts / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D000090062:Kruppel-Like Factor 4; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic
C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D014157:Transcription Factors; D049452:Green Fluorescent Proteins