Elucidation of the mechanism by which α-glucosylrutin activates human iPS cells
-Expectations for clarification of stem cell functions and further application to cosmetics-
TAKARA BELMONT Co. Rise into beauty, Walk into life. Ltd. (Headquarters: Osaka City Chuo (Hidetaka Yoshikawa, Representative Director, Chairman and President) conducted joint research with Assistant Professor Mikio Shimada of the Tokyo Institute of Technology's Institute of Science and Technology's Zero Carbon Energy Research Institute and others, to determine whether α-glucosylrutin (αG-rutin) can be used in human iPS cells. has been shown to activate the metabolism of
[Key points]
- Comparison of the effects of αG rutin (a compound with increased water solubility of the natural compound rutin) on fibroblasts, iPS cells, and iPS cell-derived epidermal keratinocytes.
- We discovered that αG-rutin treatment temporarily activates intracellular metabolism in iPS cells.
- We confirmed that heat shock proteins tend to increase in iPS cell-derived epidermal keratinocytes upon αG-rutin treatment.
【research summary】
αG rutin is a derivative of rutin, a natural flavonoid (*1), and has the property of being more water-soluble than rutin. For this reason, it has been used as an antioxidant and coloring agent in foods and cosmetics, but its effect on stem cells has not been clarified until now. Therefore, a research group including Researcher Tomoko Miyake of our Cosmetics Research and Development Department and Assistant Professor Mikio Shimada of the Zero Carbon Energy Research Institute of the Institute of Science and Technology, Tokyo Institute of Technology, created epidermal keratinocytes (*2) from human iPS cells. , fibroblasts (*3), iPS cells, and iPS cell-derived epidermal keratinocytes were subjected to comprehensive analysis of gene expression changes when αG-rutin was applied using a next-generation sequencer (*4). As a result, we discovered that in iPS cells, treatment with αG-rutin triggered an immediate early gene (*5) (IEG) response, leading to a temporary increase in intracellular metabolism. We also observed an increase in the expression of heat shock proteins (*6) in epidermal keratinocytes (Figure 1). Furthermore, when we investigated the effect of αG-rutin on the pluripotency (*7) of iPS cells, we found that the expression of pluripotency markers (*8) did not decrease and pluripotency was maintained. . (Figure 2). Furthermore, this study revealed for the first time the mechanism of action of αG-rutin on stem cells.

αG-rutin temporarily activated intracellular metabolism in iPS cells, and heat shock proteins (HSPs) tended to increase in epidermal keratinocytes.

Even after culturing iPS cells for 24 hours in a medium containing αG-rutin, the pluripotency markers OCT4 (green) and SSEA4 (red) are expressed, and pluripotency is maintained.
[Paper information]
This research was conducted in collaboration with Tokyo Institute of Technology and was published in the electronic version of the American international scientific journal "Stem Cell Research" on August 20, 2021.
Paper title:
α-glucosyl-rutinactivates immediate early genes in human induced pluripotent stem cells
(α-Glucosylrutin activates IEGs in human iPS cells)
author:
Tomoko Miyake, Munekazu Kuge, Yoshihisa Matsumoto, Mikio Shimada
Paper publication site:
https://www.sciencedirect.com/science/article/pii/S1873506121003585
Tokyo Institute of Technology press release:
https://www.titech.ac.jp/news/2021/061952
[Application development]
As a result of this joint research, we focused on αG-rutin and began product development. As our first application, we will launch LebeL ONE, a hair care product containing αG rutin, in Japan, and then gradually roll it out globally. We have also created beauty science and technology books and videos that summarize our technology, including this research.
LebeLONE official website:
https://www.lebel.co.jp/products/series/lebelone/
Beauty Science & Technology:
https://vimeo.com/583415190
【Glossary】
(1) Flavonoid: A compound synthesized by plants and a type of polyphenol.
(2) Epidermal keratinocytes: Cells present in the epidermis of the skin. Epidermal stem cells exist in the lowest layer of the epidermis and are an important part of the body that produce epidermal keratinocytes and form the epidermis.
(3) Fibroblasts: Cells that produce collagen, elastin, and hyaluronic acid, which are the sources of skin firmness and elasticity.
(4) Next-generation sequencer: A device that can analyze large amounts of DNA base sequences.
(5) Immediate early gene (IEG): A gene that is rapidly activated by various cell stimuli.
(6) Heat shock proteins (HSPs): Proteins that are expressed to protect cells when they receive stimuli such as heat. In addition to heat, it has also been reported to have a protective effect against ultraviolet rays, etc., and to be involved in the differentiation of epidermal keratinocytes.
(7) Pluripotency: The ability to differentiate into various types of cells (multipotency). Pluripotent stem cells have pluripotency and self-renewal ability. Pluripotent stem cells include embryonic stem cells (ES cells) and iPS cells.
(8) Pluripotency marker: A molecule expressed when pluripotent stem cells such as iPS cells are in an undifferentiated state.