Bidirectional developmental potential in reprogrammed cells with acquired pluripotency.
We recently discovered an unexpected phenomenon of somatic cell reprogramming into pluripotent cells by exposure to sublethal stimuli, which we call stimulus-triggered acquisition of pluripotency (STAP). This reprogramming does not require nuclear transfer or genetic manipulation. Here we report that reprogrammed STAP cells, unlike embryonic stem (ES) cells, can contribute to both embryonic and placental tissues, as seen in a blastocyst injection assay. Mouse STAP cells lose the ability to contribute to the placenta as well as trophoblast marker expression on converting into ES-like stem cells by treatment with adrenocorticotropic hormone (ACTH) and leukaemia inhibitory factor (LIF). In contrast, when cultured with Fgf4, STAP cells give rise to proliferative stem cells with enhanced trophoblastic characteristics. Notably, unlike conventional trophoblast stem cells, the Fgf4-induced stem cells from STAP cells contribute to both embryonic and placental tissues in vivo and transform into ES-like cells when cultured with LIF-containing medium. Taken together, the developmental potential of STAP cells, shown by chimaera formation and in vitro cell conversion, indicates that they represent a unique state of pluripotency.
1] Laboratory for Cellular Reprogramming, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan [2] Laboratory for Genomic Reprogramming, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan [3] Laboratory for Tissue Engineering and Regenerative Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Haruko
H
Obokata
Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
Yoshiki
Y
Sasai
Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
Hitoshi
H
Niwa
Genome Resource and Analysis Unit, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
Mitsutaka
M
Kadota
Genome Resource and Analysis Unit, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
Munazah
M
Andrabi
Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
Nozomu
N
Takata
Laboratory for Genomic Reprogramming, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
Mikiko
M
Tokoro
1] Laboratory for Cellular Reprogramming, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan [2] Laboratory for Genomic Reprogramming, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
Yukari
Y
Terashita
Electron Microscopy Laboratory, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
Shigenobu
S
Yonemura
Laboratory for Tissue Engineering and Regenerative Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Charles A
CA
Vacanti
1] Laboratory for Genomic Reprogramming, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan [2] Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi 400-8510, Japan.
Teruhiko
T
Wakayama
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D019070:Cell Lineage / Q000187:drug effects; D065150:Cellular Reprogramming / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics; D005260:Female; D051519:Fibroblast Growth Factor 4 / Q000494:pharmacology; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D010920:Placenta / Q000166:cytology* / Q000187:drug effects; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects
C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D053605:Leukemia Inhibitory Factor; D000324:Adrenocorticotropic Hormone