Successful differentiation to T cells, but unsuccessful B-cell generation, from B-cell-derived induced pluripotent stem cells.
Forced expression of certain transcription factors in somatic cells results in generation of induced pluripotent stem (iPS) cells, which differentiate into various cell types. We investigated T-cell and B-cell lineage differentiation from iPS cells in vitro. To evaluate the impact of iPS cell source, murine splenic B-cell-derived iPS (B-iPS) cells were generated after retroviral transduction of four transcription factors (Oct4, Sox2, Klf4 and c-Myc). B-iPS cells were identical to embryonic stem (ES) cells and mouse embryonic fibroblast (MEF)-derived iPS cells in morphology, ES cell marker expression as well as teratoma and chimera mouse formation. Both B-iPS and MEF-derived iPS cells differentiated into lymphocytes in OP9 co-culture systems. Both efficiently differentiated into T-cell lineage that produced IFN-γ on T-cell receptor stimulation. However, iPS cells including B-iPS cells were relatively resistant to B-cell lineage differentiation. One of the reasons of the failure of B-cell lineage differentiation seemed due to a defect of Pax5 expression in the differentiated cells. Therefore, current in vitro differentiation systems using iPS cells are sufficient for inducing T-cell but not B-cell lineage.
Division of Bioregulation Research, Institute of Medical Science, St Marianna University School of Medicine, Kanagawa 216-8512, Japan.
Haruka
H
Wada
Satoshi
S
Kojo
Chie
C
Kusama
Naoki
N
Okamoto
Yorino
Y
Sato
Bunpei
B
Ishizuka
Ken-ichiro
K
Seino
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics; D018920:Coculture Techniques; D018899:CpG Islands; D019175:DNA Methylation; D015870:Gene Expression; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000276:immunology; D000090062:Kruppel-Like Factor 4; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D051757:PAX5 Transcription Factor / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human