Whole-Genome DNA Methylation Analyses Revealed Epigenetic Instability in Tumorigenic Human iPS Cell-Derived Neural Stem/Progenitor Cells (original) (raw)

Journal Article

,

a

Department of Orthopedic Surgery, Keio University School of Medicine

, Shinjuku, Tokyo,

Japan

b

Department of Physiology, Keio University School of Medicine

, Shinjuku, Tokyo,

Japan

Search for other works by this author on:

,

a

Department of Orthopedic Surgery, Keio University School of Medicine

, Shinjuku, Tokyo,

Japan

Search for other works by this author on:

,

b

Department of Physiology, Keio University School of Medicine

, Shinjuku, Tokyo,

Japan

Search for other works by this author on:

,

b

Department of Physiology, Keio University School of Medicine

, Shinjuku, Tokyo,

Japan

Search for other works by this author on:

,

b

Department of Physiology, Keio University School of Medicine

, Shinjuku, Tokyo,

Japan

Search for other works by this author on:

,

a

Department of Orthopedic Surgery, Keio University School of Medicine

, Shinjuku, Tokyo,

Japan

Search for other works by this author on:

,

a

Department of Orthopedic Surgery, Keio University School of Medicine

, Shinjuku, Tokyo,

Japan

Search for other works by this author on:

,

a

Department of Orthopedic Surgery, Keio University School of Medicine

, Shinjuku, Tokyo,

Japan

Search for other works by this author on:

,

a

Department of Orthopedic Surgery, Keio University School of Medicine

, Shinjuku, Tokyo,

Japan

Search for other works by this author on:

,

a

Department of Orthopedic Surgery, Keio University School of Medicine

, Shinjuku, Tokyo,

Japan

Search for other works by this author on:

... Show more

Accepted:

09 January 2017

Published:

23 February 2017

• • Article contents
  • Figures & tables
  • Video
  • Audio
  • Supplementary Data
• Cite

Cite

Tsuyoshi Iida, Akio Iwanami, Tsukasa Sanosaka, Jun Kohyama, Hiroyuki Miyoshi, Narihito Nagoshi, Rei Kashiwagi, Yoshiaki Toyama, Morio Matsumoto, Masaya Nakamura, Hideyuki Okano, Whole-Genome DNA Methylation Analyses Revealed Epigenetic Instability in Tumorigenic Human iPS Cell-Derived Neural Stem/Progenitor Cells, Stem Cells, Volume 35, Issue 5, May 2017, Pages 1316–1327, https://doi.org/10.1002/stem.2581
Close

Navbar Search Filter Mobile Enter search term Search

Abstract

Although human induced pluripotent stem cell (hiPSC) derivatives are considered promising cellular resources for regenerative medicine, their tumorigenicity potentially limits their clinical application in hiPSC technologies. We previously demonstrated that oncogenic hiPSC-derived neural stem/progenitor cells (hiPSC-NS/PCs) produced tumor-like tissues that were distinct from teratomas. To gain insight into the mechanisms underlying the regulation of tumorigenicity in hiPSC-NS/PCs, we performed an integrated analysis using the Infinium HumanMethylation450 BeadChip array and the HumanHT-12 v4.0 Expression BeadChip array to compare the comprehensive DNA methylation and gene expression profiles of tumorigenic hiPSC-NS/PCs (253G1-NS/PCs) and non-tumorigenic cells (201B7-NS/PCs). Although the DNA methylation profiles of 253G1-hiPSCs and 201B7-hiPSCs were similar regardless of passage number, the methylation status of the global DNA methylation profiles of 253G1-NS/PCs and 201B7-NS/PCs differed; the genomic regions surrounding the transcriptional start site of the CAT and PSMD5 genes were hypermethylated in 253G1-NS/PCs but not in 201B7-NS/PCs. Interestingly, the aberrant DNA methylation profile was more pronounced in 253G1-NS/PCs that had been passaged more than 15 times. In addition, we identified aberrations in DNA methylation at the RBP1 gene locus; the DNA methylation frequency in RBP1 changed as 253G1-NS/PCs were sequentially passaged. These results indicate that different NS/PC clones have different DNA methylomes and that DNA methylation patterns are unstable as cells are passaged. Therefore, DNA methylation profiles should be included in the criteria used to evaluate the tumorigenicity of hiPSC-NS/PCs in the clinical setting.

© 2017 AlphaMed Press

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open\_access/funder\_policies/chorus/standard\_publication\_model)

You do not currently have access to this article.

Personal account

• Sign in with email/username & password
• Get email alerts
• Save searches
• Purchase content
• Activate your purchase/trial code
• Add your ORCID iD

Get help with access

Institutional access

Access to content on Oxford Academic is often provided through institutional subscriptions and purchases. If you are a member of an institution with an active account, you may be able to access content in one of the following ways:

IP based access

Typically, access is provided across an institutional network to a range of IP addresses. This authentication occurs automatically, and it is not possible to sign out of an IP authenticated account.

Sign in through your institution

Choose this option to get remote access when outside your institution. Shibboleth/Open Athens technology is used to provide single sign-on between your institution’s website and Oxford Academic.

1. Click Sign in through your institution.
2. Select your institution from the list provided, which will take you to your institution's website to sign in.
3. When on the institution site, please use the credentials provided by your institution. Do not use an Oxford Academic personal account.
4. Following successful sign in, you will be returned to Oxford Academic.

If your institution is not listed or you cannot sign in to your institution’s website, please contact your librarian or administrator.

Sign in with a library card

Enter your library card number to sign in. If you cannot sign in, please contact your librarian.

Society Members

Society member access to a journal is achieved in one of the following ways:

Sign in through society site

Many societies offer single sign-on between the society website and Oxford Academic. If you see ‘Sign in through society site’ in the sign in pane within a journal:

1. Click Sign in through society site.
2. When on the society site, please use the credentials provided by that society. Do not use an Oxford Academic personal account.
3. Following successful sign in, you will be returned to Oxford Academic.

If you do not have a society account or have forgotten your username or password, please contact your society.

Sign in using a personal account

Some societies use Oxford Academic personal accounts to provide access to their members. See below.

Personal account

A personal account can be used to get email alerts, save searches, purchase content, and activate subscriptions.

Some societies use Oxford Academic personal accounts to provide access to their members.

Viewing your signed in accounts

Click the account icon in the top right to:

• View your signed in personal account and access account management features.
• View the institutional accounts that are providing access.

Signed in but can't access content

Oxford Academic is home to a wide variety of products. The institutional subscription may not cover the content that you are trying to access. If you believe you should have access to that content, please contact your librarian.

Institutional account management

For librarians and administrators, your personal account also provides access to institutional account management. Here you will find options to view and activate subscriptions, manage institutional settings and access options, access usage statistics, and more.

Purchase

Short-term Access

To purchase short-term access, please sign in to your personal account above.

Don't already have a personal account? Register

Whole-Genome DNA Methylation Analyses Revealed Epigenetic Instability in Tumorigenic Human iPS Cell-Derived Neural Stem/Progenitor Cells - 24 Hours access

EUR €51.00

GBP £44.00

USD $55.00

Rental

This article is also available for rental through DeepDyve.

Citations

Views

Altmetric

Metrics

Total Views 633

451 Pageviews

182 PDF Downloads

Since 1/1/2022

Citations

33 Web of Science

×

Email alerts

Citing articles via

• Latest

• Most Read

• Most Cited

More from Oxford Academic