Pluripotency of reprogrammed somatic genomes in embryonic stem hybrid cells.
Somatic nuclei can be epigenetically reprogrammed by factors present in undifferentiated embryonic stem (ES) cells. The acquisition of pluripotency by somatic genomes could render such cells a viable source of personalized cell type(s) for therapeutic application, avoiding the need for controversial therapeutic cloning. To investigate this possibility, we first determined the origin of transcripts in teratomas generated from mouse (ES x somatic cell) hybrid clones. Transcription of markers from the somatic genome demonstrated efficient in vivo differentiation down independent lineages. The induction of dopaminergic neurons by coculture with stromal PA6 feeder cells also demonstrated efficient capacity to differentiate in vitro. Hybrid clone-derived neurons expressed appropriate markers, and transcription of Pitx3 from the somatic genome was confirmed. When transplanted into mouse brains, the dopaminergic neurons were successfully integrated and expressed tyrosine hydroxylase. Thus, it should be possible to produce personalized ES-like cells with the reprogrammed somatic genomes.
Tada
Masako
M
Department of Development and Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan.
Morizane
Asuka
A
Kimura
Hironobu
H
Kawasaki
Hiroshi
H
Ainscough
Justin F X
JF
Sasai
Yoshiki
Y
Nakatsuji
Norio
N
Tada
Takashi
T
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D017931:DNA Primers; D004298:Dopamine / Q000378:metabolism; D004586:Electrophoresis; D044127:Epigenesis, Genetic / Q000235:genetics; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics; D006822:Hybrid Cells; D007150:Immunohistochemistry; D007621:Karyotyping; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D039904:Pluripotent Stem Cells; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D033581:Stem Cell Transplantation; D013724:Teratoma / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D017931:DNA Primers; D018398:Homeodomain Proteins; D014157:Transcription Factors; C433629:homeobox protein PITX3; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine