Skip to main content
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian
  • Log in
  • My Cart

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses

New Research In

Physical Sciences

Featured Portals

  • Physics
  • Chemistry
  • Sustainability Science

Articles by Topic

  • Applied Mathematics
  • Applied Physical Sciences
  • Astronomy
  • Computer Sciences
  • Earth, Atmospheric, and Planetary Sciences
  • Engineering
  • Environmental Sciences
  • Mathematics
  • Statistics

Social Sciences

Featured Portals

  • Anthropology
  • Sustainability Science

Articles by Topic

  • Economic Sciences
  • Environmental Sciences
  • Political Sciences
  • Psychological and Cognitive Sciences
  • Social Sciences

Biological Sciences

Featured Portals

  • Sustainability Science

Articles by Topic

  • Agricultural Sciences
  • Anthropology
  • Applied Biological Sciences
  • Biochemistry
  • Biophysics and Computational Biology
  • Cell Biology
  • Developmental Biology
  • Ecology
  • Environmental Sciences
  • Evolution
  • Genetics
  • Immunology and Inflammation
  • Medical Sciences
  • Microbiology
  • Neuroscience
  • Pharmacology
  • Physiology
  • Plant Biology
  • Population Biology
  • Psychological and Cognitive Sciences
  • Sustainability Science
  • Systems Biology
Research Article

Human neural crest cells contribute to coat pigmentation in interspecies chimeras after in utero injection into mouse embryos

Malkiel A. Cohen, Katherine J. Wert, Johanna Goldmann, Styliani Markoulaki, Yosef Buganim, Dongdong Fu, and Rudolf Jaenisch
PNAS first published January 25, 2016; https://doi.org/10.1073/pnas.1525518113
Malkiel A. Cohen
aWhitehead Institute for Biomedical Research, Cambridge, MA 02142;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katherine J. Wert
aWhitehead Institute for Biomedical Research, Cambridge, MA 02142;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Johanna Goldmann
aWhitehead Institute for Biomedical Research, Cambridge, MA 02142;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Styliani Markoulaki
aWhitehead Institute for Biomedical Research, Cambridge, MA 02142;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yosef Buganim
aWhitehead Institute for Biomedical Research, Cambridge, MA 02142;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dongdong Fu
aWhitehead Institute for Biomedical Research, Cambridge, MA 02142;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rudolf Jaenisch
aWhitehead Institute for Biomedical Research, Cambridge, MA 02142;
bDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: jaenisch@wi.mit.edu
  1. Contributed by Rudolf Jaenisch, December 30, 2015 (sent for review December 6, 2015; reviewed by Nissim Benvenisty and Juan Carlos Izpisua Belmonte)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Significance

We generated mouse–human neural crest chimeras by introducing neural crest cells derived from human embryonic stem cells or induced pluripotent stem cells (iPSCs) in utero into the gastrulating mouse embryo. The cells migrated in the embryo along normal migration routes and contributed to functional pigment cells in the postnatal animal, as demonstrated by coat color contribution. This experimental system represents a novel paradigm that allows studying the developmental potential of human cells under in vivo conditions. Importantly, this platform will allow for the investigation of human diseases in the animal by using patient-derived iPSCs.

Abstract

The neural crest (NC) represents multipotent cells that arise at the interphase between ectoderm and prospective epidermis of the neurulating embryo. The NC has major clinical relevance because it is involved in both inherited and acquired developmental abnormalities. The aim of this study was to establish an experimental platform that would allow for the integration of human NC cells (hNCCs) into the gastrulating mouse embryo. NCCs were derived from pluripotent mouse, rat, and human cells and microinjected into embryonic-day-8.5 embryos. To facilitate integration of the NCCs, we used recipient embryos that carried a c-Kit mutation (Wsh/Wsh), which leads to a loss of melanoblasts and thus eliminates competition from the endogenous host cells. The donor NCCs migrated along the dorsolateral migration routes in the recipient embryos. Postnatal mice derived from injected embryos displayed pigmented hair, demonstrating differentiation of the NCCs into functional melanocytes. Although the contribution of human cells to pigmentation in the host was lower than that of mouse or rat donor cells, our results indicate that hNCCs, injected in utero, can integrate into the embryo and form mature functional cells in the animal. This mouse–human chimeric platform allows for a new approach to study NC development and diseases.

  • human neural crest cells
  • chimera
  • embryonic stem cells
  • melanocytes

Footnotes

  • ↵1Present address: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.

  • ↵2To whom correspondence should be addressed. Email: jaenisch{at}wi.mit.edu.
  • Author contributions: M.A.C. and R.J. designed research; M.A.C. performed research; K.J.W., J.G., S.M., Y.B., and D.F. contributed new reagents/analytic tools; M.A.C. and K.J.W. analyzed data; and M.A.C., K.J.W., and R.J. wrote the paper.

  • Reviewers: N.B., The Hebrew University of Jerusalem; and J.C.I.B., The Salk Institute for Biological Studies.

  • The authors declare no conflict of interest.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1525518113/-/DCSupplemental.

http://www.pnas.org/preview_site/misc/userlicense.xhtml

Next
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Human neural crest cells contribute to coat pigmentation in interspecies chimeras after in utero injection into mouse embryos
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Human NCCs contribute to interspecies chimeras
Malkiel A. Cohen, Katherine J. Wert, Johanna Goldmann, Styliani Markoulaki, Yosef Buganim, Dongdong Fu, Rudolf Jaenisch
Proceedings of the National Academy of Sciences Jan 2016, 201525518; DOI: 10.1073/pnas.1525518113

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Human NCCs contribute to interspecies chimeras
Malkiel A. Cohen, Katherine J. Wert, Johanna Goldmann, Styliani Markoulaki, Yosef Buganim, Dongdong Fu, Rudolf Jaenisch
Proceedings of the National Academy of Sciences Jan 2016, 201525518; DOI: 10.1073/pnas.1525518113
Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley
Proceedings of the National Academy of Sciences: 118 (8)
Current Issue

Submit

Sign up for Article Alerts

Jump to section

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Surgeons hands during surgery
Inner Workings: Advances in infectious disease treatment promise to expand the pool of donor organs
Despite myriad challenges, clinicians see room for progress.
Image credit: Shutterstock/David Tadevosian.
Setting sun over a sun-baked dirt landscape
Core Concept: Popular integrated assessment climate policy models have key caveats
Better explicating the strengths and shortcomings of these models will help refine projections and improve transparency in the years ahead.
Image credit: Witsawat.S.
Double helix
Journal Club: Noncoding DNA shown to underlie function, cause limb malformations
Using CRISPR, researchers showed that a region some used to label “junk DNA” has a major role in a rare genetic disorder.
Image credit: Nathan Devery.
Steamboat Geyser eruption.
Eruption of Steamboat Geyser
Mara Reed and Michael Manga explore why Yellowstone's Steamboat Geyser resumed erupting in 2018.
Listen
Past PodcastsSubscribe
Multi-color molecular model
Enzymatic breakdown of PET plastic
A study demonstrates how two enzymes—MHETase and PETase—work synergistically to depolymerize the plastic pollutant PET.
Image credit: Aaron McGeehan (artist).

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Special Feature Articles – Most Recent
  • List of Issues

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Librarians
  • Press
  • Site Map
  • PNAS Updates

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490