A neurosphere-derived factor, cystatin C, supports differentiation of ES cells into neural stem cells

Takeo Kato, Toshio Heike, Katsuya Okawa, Munetada Haruyama, Kazuhiro Shiraishi, Momoko Yoshimoto, Masako Nagato, Minoru Shibata, Tomohiro Kumada, Yasunari Yamanaka, Haruo Hattori, Tatsutoshi Nakahata

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Although embryonic stem (ES) cells are capable of unlimited proliferation and pluripotent differentiation, effective preparation of neural stem cells from ES cells are not achieved. Here, we have directly generated under the coculture with dissociated primary neurosphere cells in serum-free medium and the same effect was observed when ES cells were cultured with conditioned medium of primary neurosphere culture (CMPNC). ES-neural stem cells (NSCs) could proliferate for more than seven times and differentiate into neurons, astrocytes, and oligodendrocytes in vitro and in vivo. The responsible molecule in CMPNC was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, which turned out to be cystatin C. Purified cystatin C in place of the CMPNC could generate ES-NSCs efficiently with self-renewal and multidifferentiation potentials. These results reveal the validity of cystatin C for generating NSCs from ES cells.

Original languageEnglish (US)
Pages (from-to)6019-6024
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number15
DOIs
StatePublished - Apr 11 2006

Keywords

  • Coculture system
  • Conditioned medium of primary neurosphere culture

ASJC Scopus subject areas

  • General

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    Kato, T., Heike, T., Okawa, K., Haruyama, M., Shiraishi, K., Yoshimoto, M., Nagato, M., Shibata, M., Kumada, T., Yamanaka, Y., Hattori, H., & Nakahata, T. (2006). A neurosphere-derived factor, cystatin C, supports differentiation of ES cells into neural stem cells. Proceedings of the National Academy of Sciences of the United States of America, 103(15), 6019-6024. https://doi.org/10.1073/pnas.0509789103