Laboratories

Stem Cell Technologies

Prof. Kurisaki
Professor
Akira KURISAKI
Assistant Professor
Hitomi TAKADA

Outline of Research and Education

Pluripotent stem cells, such as embryonic stem (ES) cells and induced pluripotent stem (iPS) cells, have abilities of unlimited self-renewal and multiple differentiations into all the tissue cells of the body. Therefore, these stem cells find potential application in regenerative medicine and drug discovery, and it is very important to strictly regulate this potent differentiation ability to induce multi-step differentiation of these stem cells toward functional tissue cells. During mammalian development, cells differentiate to form precise 3D structures of organs. Understanding of this process could contribute to the development of in vitro differentiation methods. Our goal is to understand the mechanisms of stomach and lung development to perform in vitro differentiation of pluripotent stem cells into these tissue cells. Moreover, we plan to develop in vitro disease models of these organs and technologies for regenerative medicine in the near future.

Major Research Topics

Generation of gastric tissues and their disease models

Although the stomach is a major organ in our body, the mechanisms of development of this organ are not well known. During early development, a primitive gastric tube developed from early endoderm is converted to stomach primordium, and further matures to fundus and antrum tissues covered with gastric glands. Recently, we developed an in vitro differentiation method of mouse ES cells to whole stomach tissue (Fig.1). We think that this method could be a powerful tool to study the mechanisms of stomach development as well as serve as a unique model for various diseases such as gastric cancer (Fig.2). We are currently investigating the mechanisms of gastrointestinal development, and studying these mechanisms using our in vitro model.

Differentiation of lung tissue and tissue regeneration

The lung emerges as lung buds from early gastric tube during development. These primordia proliferate, morphologically divide into multiple branches with the mesenchymal layer, and further differentiate into several kinds of epithelial cells to fulfill respiratory functions (Fig.3). Recently, differentiation methods for these lung tissues have been investigated in the scientific community. We are also studying novel differentiation methods for these respiratory tissues.

Stem cells in tumor

Pancreatic cancer has a low survival rate because of a lack of early detectable symptoms and poor prognosis. Recent observations suggested the presence of a small number of stem cells in various cancers, which hamper effective cancer therapy. In our laboratory, we study regulatory mechanisms of these cancer stem cells to decrease their functional potential.

References

  1. Noguchi TK et al., Nature Cell Biology, 17, 984-993, 2015
  2. Watanabe-Susaki K et al., Stem Cells, 32, 3099-3111, 2014
  3. Seki Y et al., Proc. Natl. Acad. Sci. U S A, 107, 10926-10931, 2010
  4. Nakanishi M et al., FASEB J, 23, 114-122, 2009
  5. Satow R et al., Developmental Cell, 11, 763-774, 2006
  6. Kurisaki A et al., Mol. Cell. Biol., 26, 1318-1332, 2006
  7. Kurisaki A et al., Mol. Biol. Cell, 12,1079-1091, 2001
Fig.1
Fig.1 Stomach tissue differentiated from mouse ES cells in vitro by 3D culture method. (Left) HE staining of the differentiated stomach organoid (day 56). (Right) Immunofluorescent staining of stomach organoid with Epcam antibody (red), Desmin antibody (green), and DAPI (blue) for epidermis, mesenchyme, and nuclei, respectively. Stomach organoid with gastric glands and mesenchyme can be differentiated from ES cells in vitro.
Fig.2
Fig.2 A stomach disease model using in vitro differentiation method. (Left) Healthy control model. (Right) Ménétrier's disease model with massive gastric folds. This disease model can be generated by addition of TGF-α after day 28 of in vitro differentiation.
Fig.3
Fig.3 During lung development, lung progenitor cells are generated in lung buds and can differentiate into various functional epithelial cells of the lung. These lung progenitor cells can be differentiated from pluripotent stem cells in vitro.
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