Stress creёert pluripotente stam cellen Extracellular stress makes

Innovatie Attaché Tokio
Kugako Sugimoto, February 5, 2014, meer informatie:
Stress creёert pluripotente stam cellen
Extracellular stress makes somatic cells into pluripotent cells
RIKEN, de grootste japanse researchorganisatie voor fundamenteel en toegepast onderzoek,
heeft de ontwikkeling bekend gemaakt van Stimulus Triggered Acquisition van Pluripotente
(STAP) cellen. Deze cellen verkrijgen hun pluripotentie door extracellulaire stress,
bijvoorbeeld wanneer lichaamscellen in vitro worden blootgesteld aan zure omstandigheden
Deze procedure maakt geen gebruik van genetische manipulatie. STAP cellen die ingebracht
zijn in muizen leveren embryonale cellen die zich vermenigvuldigen en maar ook cellen die
in de placenta groeien
RIKEN announced development of Stimulus-Triggered Acquisition of Pluripotency cells (STAP
cells). STAP cells obtained pluripotency by receiving extracellular stress such as acidic
condition to somatic cells in vitro. This procedure did not require genetic manipulation. STAP
cells planted in mice were able to rise not only embryonic cells but also extraembryonic cells
such as placental tissue.
Joint work by Dr. Haruko Obokata of RIKEN, Dr. Charles Vacanti of Harvard University, and
other researchers was published in Nature on January 30, 2014 on the development of the
Stimulus-Triggered Acquisition of Pluripotency cells (STAP cells). The technology of creating
of STAP cells with induced pluripotency needed extracellular stress to somatic cells in a tube.
The research group used mouse splenic CD45+* cells as somatic cells. These cells were
exposed to low-pH solution, pH 5.7, at 37 ℃ for 30 min and then cultured in a solution with
leukemia inhibitory factor (LIF). LIF is a factor to maintain pluripotency. After 2 days, cells
started to express Oct4, gene specific for pluripotent cells. Expression of Oct4 was observed
through GFP that illuminates associated with the expression of Oct4 gene. Oct4-expressed
cells were small and tended to make aggregates after 7 days of the treatment.
To eliminate the possibility of contamination of the culture, real time observation to follow
the development of the stress-treated cells to Oct4-expressed cells was used. Furthermore,
gene analysis of Oct4-expressed cells was conducted because splenic CD45+ shows the
unique recombination of genes of T cell receptor through their differentiation. These
observations showed the Oct4-expressed cells originated from the stress-exposed mouse
splenic CD45+ cells.
Furthermore, the Oct4-expressed cells also expressed genes specific for pluripotent cells
such as Sox2**, SSEA1, Nanog***. In addition, methylation status was not characteristic for
a lymphocytes but a pluripotent cell.
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3-6-3 Shibakoen, Minato-ku, Tokyo 105-0011, Japan | T:+81-3-5776-5510 | F:+81-3-5776-5534 | [email protected]
Oct4-expressed cells showed the ability to form a chimera embryo as well as placental
tissues in a blastocyst injection assay. ES cells and iPS cells are known to form chimera
embryos but not placental tissues, which indicates the Oct4-expressed cells further
“undifferentiated” compared to ES cells and iPS cells. When STAP cells were treated with
Fibroblast Growth Factor 4 (FGF4), a growth factor, the tendency to differentiate to placental
tissues increased.
Compared to iPS cells, the self-renewal capacity of STAP cells was limited. If STAP cells were
cultured with the solution containing adrenocorticotropic hormone (ACTH) that RIKEN
developed, the self-renewal capacity increased. However, differentiation to the placental
tissues did not occur for these cells, while a chimera mouse was formed.
Other types of somatic cells were also tested whether they showed pluripotency through
exposure to low-pH. Cells from brain, skin, lung, liver, skeletal muscle, adipose tissue, and
heart muscle showed that they obtained pluripotency on one level or another.
Other types of sublethal extracellular stress such as mixing and exposure to streptolysin O to
make holes on the membrane also induced STAP cells.
Dedifferentiation of somatic cell to STAP cells occurred fast. It took only 2 days to start
expressing signs of differentiation. In addition, nuclear transfer and genetic manipulation
were not required in the process. It is expected that this technology can be used for human
cells as well as for understanding the mechanisms of dedifferentiation.
1. Obokata H, et al., Nature (2014) vol 505, p676-680
2. RIKEN Press Release Jan. 30, 2014 (in Japanese)
*CD45 (Wikipedia)
**Sox2 (Wikipedia)
***Nanog (Wikipedia)
Sublethal stress to somatic cells turns into pluripotent cells.
-----NOST Tokyo | Embassy of the Kingdom of the Netherlands
3-6-3 Shibakoen, Minato-ku, Tokyo 105-0011, Japan | T:+81-3-5776-5510 | F:+81-3-5776-5534 | [email protected]