Modeling Familial Cancer with Induced Pluripotent Stem Cells | Zendy

DungFang Lee | Zendy; Jie Su | Zendy; Huen Suk Kim | Zendy; Betty Chang | Zendy; Dmitri Papatsenko | Zendy; Ruiying Zhao | Zendy; Ye Yuan | Zendy; Julian A. Gingold | Zendy; Weiya Xia | Zendy; Henia Darr | Zendy; Razmik Mirzayans | Zendy; MienChie Hung | Zendy; Christoph Schaniel | Zendy; Ihor R. Lemischka | Zendy

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Modeling Familial Cancer with Induced Pluripotent Stem Cells

Author(s) -

DungFang Lee,

Jie Su,

Huen Suk Kim,

Betty Chang,

Dmitri Papatsenko,

Ruiying Zhao,

Ye Yuan,

Julian A. Gingold,

Weiya Xia,

Henia Darr,

Razmik Mirzayans,

MienChie Hung,

Christoph Schaniel,

Ihor R. Lemischka

Publication year - 2015

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2015.02.045

Subject(s) - induced pluripotent stem cell , biology , downregulation and upregulation , cancer research , microbiology and biotechnology , cancer , osteosarcoma , stem cell , gene , embryonic stem cell , genetics

In vitro modeling of human disease has recently become feasible with induced pluripotent stem cell (iPSC) technology. Here, we established patient-derived iPSCs from a Li-Fraumeni syndrome (LFS) family and investigated the role of mutant p53 in the development of osteosarcoma (OS). LFS iPSC-derived osteoblasts (OBs) recapitulated OS features including defective osteoblastic differentiation as well as tumorigenic ability. Systematic analyses revealed that the expression of genes enriched in LFS-derived OBs strongly correlated with decreased time to tumor recurrence and poor patient survival. Furthermore, LFS OBs exhibited impaired upregulation of the imprinted gene H19 during osteogenesis. Restoration of H19 expression in LFS OBs facilitated osteoblastic differentiation and repressed tumorigenic potential. By integrating human imprinted gene network (IGN) into functional genomic analyses, we found that H19 mediates suppression of LFS-associated OS through the IGN component DECORIN (DCN). In summary, these findings demonstrate the feasibility of studying inherited human cancer syndromes with iPSCs.

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