Establishment of Tsc2‑deficient rat embryonic stem cells

  • Authors:
    • Yoshitaka Ito
    • Haruna Kawano
    • Fumio Kanai
    • Eri Nakamura
    • Norihiro Tada
    • Setsuo Takai
    • Shigeo Horie
    • Hajime Arai
    • Toshiyuki Kobayashi
    • Okio Hino
  • View Affiliations

  • Published online on: March 3, 2015     https://doi.org/10.3892/ijo.2015.2913
  • Pages: 1944-1952
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Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by TSC1 or TSC2 mutations. TSC causes the development of tumors in various organs such as the brain, skin, kidney, lung, and heart. The protein complex TSC1/2 has been reported to have an inhibitory function on mammalian target of rapamycin complex 1 (mTORC1). Treatment with mammalian target of rapamycin (mTOR) inhibitors has demonstrated tumor‑reducing effects in patients with TSC but is also associated with various adverse effects. In recent years, experiments involving in vivo differentiation of pluripotent stem cells have been reported as useful in elucidating mechanisms of pathogenesis and discovering new therapeutic targets for several diseases. To reveal the molecular basis of the pathogenesis caused by the Tsc2 mutation, we derived embryonic stem cells (ESCs) from Eker rats, which have the Tsc2 mutation and develop brain lesions and renal tumors. Although several studies have reported the necessity of Tsc1 and Tsc2 regulation to maintain ESCs and hematopoietic stem cells, we successfully established not only Tsc2+/+ and Tsc2+/- ESCs but also Tsc2-/- ESCs. We confirmed that these cells express pluripotency markers and retain the ability to differentiate into all three germ layers. Comprehensive gene expression analysis of Tsc2+/+ and Tsc2+/- ESCs revealed similar profiles, whereas the profile of Tsc2-/- ESCs was distinct from these two. In vitro differentiation experiments using these ESCs combined with in vivo experiments may reveal the mechanism of the tissue‑specific pathogenesis caused by the Tsc2 mutation and identify specific new therapeutic targets.
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May 2015
Volume 46 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Ito, Y., Kawano, H., Kanai, F., Nakamura, E., Tada, N., Takai, S. ... Hino, O. (2015). Establishment of Tsc2‑deficient rat embryonic stem cells. International Journal of Oncology, 46, 1944-1952. https://doi.org/10.3892/ijo.2015.2913
MLA
Ito, Y., Kawano, H., Kanai, F., Nakamura, E., Tada, N., Takai, S., Horie, S., Arai, H., Kobayashi, T., Hino, O."Establishment of Tsc2‑deficient rat embryonic stem cells". International Journal of Oncology 46.5 (2015): 1944-1952.
Chicago
Ito, Y., Kawano, H., Kanai, F., Nakamura, E., Tada, N., Takai, S., Horie, S., Arai, H., Kobayashi, T., Hino, O."Establishment of Tsc2‑deficient rat embryonic stem cells". International Journal of Oncology 46, no. 5 (2015): 1944-1952. https://doi.org/10.3892/ijo.2015.2913