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Development. 2018 Aug 23;145(16). pii: dev165431. doi: 10.1242/dev.165431.

Modeling human somite development and fibrodysplasia ossificans progressiva with induced pluripotent stem cells.

Author information

1
Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.
2
Department of Tissue Regeneration, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
3
Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.
4
Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
5
Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan mikeya@cira.kyoto-u.ac.jp.

Abstract

Somites (SMs) comprise a transient stem cell population that gives rise to multiple cell types, including dermatome (D), myotome (MYO), sclerotome (SCL) and syndetome (SYN) cells. Although several groups have reported induction protocols for MYO and SCL from pluripotent stem cells, no studies have demonstrated the induction of SYN and D from SMs. Here, we report systematic induction of these cells from human induced pluripotent stem cells (iPSCs) under chemically defined conditions. We also successfully induced cells with differentiation capacities similar to those of multipotent mesenchymal stromal cells (MSC-like cells) from SMs. To evaluate the usefulness of these protocols, we conducted disease modeling of fibrodysplasia ossificans progressiva (FOP), an inherited disease that is characterized by heterotopic endochondral ossification in soft tissues after birth. Importantly, FOP-iPSC-derived MSC-like cells showed enhanced chondrogenesis, whereas FOP-iPSC-derived SCL did not, possibly recapitulating normal embryonic skeletogenesis in FOP and cell-type specificity of FOP phenotypes. These results demonstrate the usefulness of multipotent SMs for disease modeling and future cell-based therapies.

KEYWORDS:

Differentiation; Disease modeling; Fibrodysplasia ossificans progressiva; Induced pluripotent stem cells; Paraxial mesoderm

PMID:
30139810
PMCID:
PMC6124548
DOI:
10.1242/dev.165431
[Indexed for MEDLINE]
Free PMC Article

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