Establishment of a Gorlin syndrome model from induced neural progenitor cells exhibiting constitutive GLI1 expression and high sensitivity to inhibition by smoothened (SMO)

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The hedgehog signaling pathway is a vital factor for embryonic development and stem cell maintenance. Dysregulation of its function results in tumor initiation and progression. The aim of this research was to establish a disease model of hedgehog-related tumorigenesis with Gorlin syndrome-derived induced pluripotent stem cells (GS-iPSCs). Induced neural progenitor cells from GS-iPSCs (GS-NPCs) show constitutive high GLI1 expression and higher sensitivity to smoothened (SMO) inhibition compared with wild-type induced neural progenitor cells (WT-NPCs). The differentiation process from iPSCs to NPCs may have similarity in gene expression to Hedgehog signal-related carcinogenesis. Therefore, GS-NPCs may be useful for screening compounds to find effective drugs to control Hedgehog signaling activity.

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We thank Dr Hideki Uchikawa, Dr Tadashi Shiohama, Dr Tomoko Uchida, and Dr Hiromi Aoyama for technical support and critical review of this study. This work was supported by JSPS KAKENHI Grant Number 16K09960; Chiba University VBL Research Project Grant Number 2018-002; Medical and Welfare Network Chiba Project Grant Number 2018-001.


JSPS KAKENHI Grant Number 16K09960; Chiba University VBL Research Project Grant Number 2018-002; Medical and Welfare Network Chiba Project Grant Number 2018-001.

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Correspondence to Akihiro Umezawa.

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The authors declare that they have no conflict of interest.

Ethics statement

This study was approved by Ethics committee of Chiba University Graduate School of Medicine (#2017 - 792), and the Institutional Review Board of the National Center for Child Health and Development of Japan (#884). We obtained informed consent from each patient with Gorlin syndrome. Animal experiments were performed according to the protocols approved by the Institutional Animal Care and Use Committee of the National Research Institute for Child Health and Development (A2003-002-C15-M06).

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Ikehara, H., Fujii, K., Miyashita, T. et al. Establishment of a Gorlin syndrome model from induced neural progenitor cells exhibiting constitutive GLI1 expression and high sensitivity to inhibition by smoothened (SMO). Lab Invest (2019) doi:10.1038/s41374-019-0346-2

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  • induced pluripotent stem cells
  • hedgehog signaling pathway
  • PTCH1
  • GLI1
  • vismodegib