Transient activation of<i>c-MYC</i>expression is critical for efficient platelet generation from human induced pluripotent stem cells

Takayama, Nobuki; Nishimura, Satoshi; Nakamura, Sou; Shimizu, Takafumi; Ohnishi, Ryoko; Endô, Hiroshi; Yamaguchi, Tomoyuki; Otsu, Makoto; Nishimura, Ken; Nakanishi, Mahito; Sawaguchi, Akira; Nagai, Ryozo; Takahashi, Kazutoshi; Yamanaka, Shinya; Nakauchi, Hiromitsu; Eto, Koji

doi:10.1083/jcb1915oia11

Cited by 50 publications

(105 citation statements)

References 1 publication

Supporting

Mentioning

103

Contrasting

Order By: Relevance

“…[20][21][22] These iPS cell-derived organs demonstrate a similar capacity to naive organs. Senju et al 13 examined the global gene expression profiles of BMDCs and iPSDCs using DNA microarrays.…”

Section: Discussionmentioning

confidence: 94%

Antitumor immune response of dendritic cells (DCs) expressing tumor‐associated antigens derived from induced pluripotent stem cells: In comparison to bone marrow‐derived DCs

Iwamoto

Ojima

Hayata

et al. 2013

Intl Journal of Cancer

View full text Add to dashboard Cite

It is generally accepted that the difficulty in obtaining a sufficient number of functional dendritic cells (DCs) is a serious problem in DC-based immunotherapy. Therefore, we used the induced pluripotent stem (iPS) cell-derived DCs (iPSDCs). If the therapeutic efficacy of iPSDCs is equivalent to that of bone marrow-derived DCs (BMDCs), then the aforementioned problems may be solved. In our study, we induced iPSDCs from iPS cells and examined the capacity for maturation of iPSDCs compared to that of BMDCs in addition to the capacity for migration of iPSDCs to regional lymph nodes. We adenovirally transduced the hgp100 gene, natural tumor antigens, into DCs and immunized mice once with the genetically modified DCs. The cytotoxic activity of CD8 (1) cytotoxic T lymphocytes (CTLs) was assayed using a 51 Cr-release assay. The therapeutic efficacy of the vaccination was examined in a subcutaneous tumor model. Our results showed that iPSDCs have an equal capacity to BMDCs in terms of maturation and migration. Furthermore, hgp100-specific CTLs were generated in mice immunized with genetically modified iPSDCs. These CTLs exhibited as high a level of cytotoxicity against B16 cells as BMDCs. Moreover, vaccination with the genetically modified iPSDCs achieved as high a level of therapeutic efficacy as vaccination with BMDCs. Our study clarified experimentally that genetically modified iPSDCs have an equal capacity to BMDCs in terms of tumor-associated antigenspecific therapeutic antitumor immunity. This vaccination strategy may therefore be useful for future clinical application as a cancer vaccine.

show abstract

Section: Discussionmentioning

confidence: 94%

Antitumor immune response of dendritic cells (DCs) expressing tumor‐associated antigens derived from induced pluripotent stem cells: In comparison to bone marrow‐derived DCs

Iwamoto

Ojima

Hayata

et al. 2013

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…The SCN-iPS cells, as well as control iPS cells that were generated from healthy donors, had the normal karyotype ( Fig. S1E) (10,11) and no mutations in the mutation-sensitive region of the G-CSF receptor gene (12).…”

Section: Resultsmentioning

confidence: 99%

Wnt3a stimulates maturation of impaired neutrophils developed from severe congenital neutropenia patient-derived pluripotent stem cells

Hiramoto

Ebihara

Mizoguchi

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

The derivation of induced pluripotent stem (iPS) cells from individuals of genetic disorders offers new opportunities for basic research into these diseases and the development of therapeutic compounds. Severe congenital neutropenia (SCN) is a serious disorder characterized by severe neutropenia at birth. SCN is associated with heterozygous mutations in the neutrophil elastase [elastase, neutrophil-expressed (ELANE)] gene, but the mechanisms that disrupt neutrophil development have not yet been clarified because of the current lack of an appropriate disease model. Here, we generated iPS cells from an individual with SCN (SCN-iPS cells). Granulopoiesis from SCN-iPS cells revealed neutrophil maturation arrest and little sensitivity to granulocyte-colony stimulating factor, reflecting a disease status of SCN. Molecular analysis of the granulopoiesis from the SCN-iPS cells vs. control iPS cells showed reduced expression of genes related to the wingless-type mmtv integration site family, member 3a (Wnt3a)/β-catenin pathway [e.g., lymphoid enhancer-binding factor 1], whereas Wnt3a administration induced elevation lymphoid enhancer-binding factor 1-expression and the maturation of SCN-iPS cell-derived neutrophils. These results indicate that SCN-iPS cells provide a useful disease model for SCN, and the activation of the Wnt3a/β-catenin pathway may offer a novel therapy for SCN with ELANE mutation.

show abstract

“…Transplantation of these differentiated cells is expected to result in functional recovery in patients. In fact, the transplantation of differentiated cells derived from iPS cells has already been shown to mitigate the disease phenotypes in mouse models of sickle cell anemia, 77) platelet deficiency, 78) Parkinson's disease 79) and spinal cord injury. 80),81) iPS cells can be generated from patients' own somatic cells.…”

Section: Medical and Pharmaceutical Applications Of Ips Cellsmentioning

confidence: 99%

Induction of pluripotency by defined factors

Okita

Yamanaka

2010

Experimental Cell Research

Self Cite

View full text Add to dashboard Cite

Abstract:The "reversion of cell fate from differentiated states back into totipotent or pluripotent states" has been an interest of many scientists for a long time. With the help of knowledge accumulated by those scientists, we succeeded in converting somatic cells to a pluripotent cell lineage by the forced expression of defined factors. These established induced pluripotent stem (iPS) cells have similar features to embryonic stem (ES) cells, including pluripotency and immortality. The iPS cell technology provides unprecedented opportunities for regenerative medicine and drug discovery.

show abstract

Transient activation ofc-MYCexpression is critical for efficient platelet generation from human induced pluripotent stem cells

Cited by 50 publications

References 1 publication

Antitumor immune response of dendritic cells (DCs) expressing tumor‐associated antigens derived from induced pluripotent stem cells: In comparison to bone marrow‐derived DCs

Antitumor immune response of dendritic cells (DCs) expressing tumor‐associated antigens derived from induced pluripotent stem cells: In comparison to bone marrow‐derived DCs

Wnt3a stimulates maturation of impaired neutrophils developed from severe congenital neutropenia patient-derived pluripotent stem cells

Induction of pluripotency by defined factors

Contact Info

Product

Resources

About