Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Accepted manuscripts
    • Issue in progress
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Special issues
    • Subject collections
    • Sign up for alerts
  • About us
    • About Development
    • About the Node
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Workshops and Meetings
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Sign up for alerts
  • Contacts
    • Contacts
    • Subscriptions
    • Feedback
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

User menu

  • Log in

Search

  • Advanced search
Development
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

supporting biologistsinspiring biology

Development

  • Log in
Advanced search

RSS  Twitter  Facebook  YouTube 

  • Home
  • Articles
    • Accepted manuscripts
    • Issue in progress
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Special issues
    • Subject collections
    • Sign up for alerts
  • About us
    • About Development
    • About the Node
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Workshops and Meetings
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Sign up for alerts
  • Contacts
    • Contacts
    • Subscriptions
    • Feedback
STEM CELLS AND REGENERATION
Mitochondrial and glycolytic remodeling during nascent neural differentiation of human pluripotent stem cells
Jarmon G. Lees, David K. Gardner, Alexandra J. Harvey
Development 2018 145: dev168997 doi: 10.1242/dev.168997 Published 22 October 2018
Jarmon G. Lees
School of BioSciences, University of Melbourne, Parkville 3010, Victoria, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jarmon G. Lees
David K. Gardner
School of BioSciences, University of Melbourne, Parkville 3010, Victoria, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for David K. Gardner
  • For correspondence: david.gardner@unimelb.edu.au
Alexandra J. Harvey
School of BioSciences, University of Melbourne, Parkville 3010, Victoria, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alexandra J. Harvey
  • Article
  • Figures & tables
  • Supp info
  • Info & metrics
  • PDF + SI
  • PDF
Loading

ABSTRACT

As human pluripotent stem cells (hPSCs) exit pluripotency, they reportedly switch from glycolytic energy production to primarily mitochondrial metabolism. Here, we show that upon ectoderm differentiation to neural precursor cells (NPCs), hPSCs increase glycolytic rate, ultimately producing more carbon as lactate than is consumed as glucose. However, glucose, lactate and pyruvate utilization decrease to half their PSC levels by the NPC stage, establishing a more quiescent metabolic state. Furthermore, we characterize a metabolic exit event within the first 24 h of differentiation, plausibly necessary to transition hPSCs out of the pluripotent state. Contrary to current thinking, mitochondrial mass does not increase during NPC induction. Instead, mitochondrial DNA copies and mitochondrial activity decrease, suggesting that mitochondrial metabolism either requires suppression, or is not required, for nascent ectoderm differentiation. Our work, therefore, contrasts with the dogma that the hPSC state is primarily glycolytic, transitioning to an oxidative metabolism upon the loss of the pluripotent state. Instead, we show that heightened glycolytic metabolism is acquired, indicating that metabolic modulation of both glycolysis and mitochondrial metabolism occurs during exit from pluripotency in hPSCs.

Footnotes

  • Competing interests

    The authors declare no competing or financial interests.

  • Author contributions

    Conceptualization: J.G.L., A.J.H., D.K.G.; Methodology: J.G.L., A.J.H.; Software: J.G.L.; Validation: J.G.L.; Formal analysis: J.G.L.; Investigation: J.G.L.; Resources: D.K.G.; Data curation: D.K.G.; Writing - original draft: J.G.L.; Writing - review & editing: J.G.L., A.J.H., D.K.G.; Visualization: A.J.H., D.K.G.; Supervision: A.J.H., D.K.G.; Project administration: A.J.H., D.K.G.; Funding acquisition: A.J.H., D.K.G.

  • Funding

    This work was supported by the Australian Research Council Special Research Initiative Stem Cells Australia (SR110001002), and a Jasper Loftus-Hills Award (UTR7.116), an Alfred Nicholas Fellowship Award (UTR6.197), and an F. H. Drummond Travel Award (UTR6.184) from the University of Melbourne.

  • Supplementary information

    Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.168997.supplemental

  • Received June 14, 2018.
  • Accepted September 18, 2018.
http://www.biologists.com/user-licence-1-1/
View Full Text

Log in using your username and password

Forgot your user name or password?

Log in through your institution

You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password.
If your organization uses OpenAthens, you can log in using your OpenAthens username and password. To check if your institution is supported, please see this list. Contact your library for more details.

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$30.00 .

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

Previous ArticleNext Article
Back to top
Previous ArticleNext Article

This Issue

Keywords

  • Metabolism
  • Pluripotent stem cells
  • Differentiation
  • Neural precursor cell
  • Glycolysis

 Download PDF

Email

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

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.
Mitochondrial and glycolytic remodeling during nascent neural differentiation of human pluripotent stem cells
(Your Name) has sent you a message from Development
(Your Name) thought you would like to see the Development web site.
Share
STEM CELLS AND REGENERATION
Mitochondrial and glycolytic remodeling during nascent neural differentiation of human pluripotent stem cells
Jarmon G. Lees, David K. Gardner, Alexandra J. Harvey
Development 2018 145: dev168997 doi: 10.1242/dev.168997 Published 22 October 2018
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
STEM CELLS AND REGENERATION
Mitochondrial and glycolytic remodeling during nascent neural differentiation of human pluripotent stem cells
Jarmon G. Lees, David K. Gardner, Alexandra J. Harvey
Development 2018 145: dev168997 doi: 10.1242/dev.168997 Published 22 October 2018

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Alerts

Please log in to add an alert for this article.

Sign in to email alerts with your email address

Article navigation

  • Top
  • Article
    • ABSTRACT
    • INTRODUCTION
    • RESULTS AND DISCUSSION
    • MATERIALS AND METHODS
    • Footnotes
    • References
  • Figures & tables
  • Supp info
  • Info & metrics
  • PDF + SI
  • PDF

Related articles

Cited by...

More in this TOC section

  • Cell-autonomous and redundant roles of Hey1 and HeyL in muscle stem cells: HeyL requires Hes1 to bind diverse DNA sites
  • Ecrg4 deficiency extends the replicative capacity of neural stem cells in a Foxg1-dependent manner
  • BMP signaling is required for amphioxus tail regeneration
Show more STEM CELLS AND REGENERATION

Similar articles

Subject collections

  • Stem cells & regeneration
  • Human development

Other journals from The Company of Biologists

Journal of Cell Science

Journal of Experimental Biology

Disease Models & Mechanisms

Biology Open

Advertisement

The people behind the papers – Elena Popa and Abigail Tucker

Elena Popa and Abigail Tucker

“After what felt like hundreds of failed attempts, finally being able to see Sox2 staining under the microscope felt like a huge relief!”

First author Elena Popa and Abigail Tucker, Professor of Development and Evolution at King's College London, talk about their research into tooth development in the mouse and other organisms.


Spotlight - CRISPR babies: a view from the centre of the storm

Matt Porteus (right) and Robin Lovell-Badge (left) clarify some statements made by He Jiankui. Courtesy of Vivian Tam (School of Biomedical Sciences, University of Hong Kong)

Matt Porteus (right) and Robin Lovell-Badge (left) clarify some statements made by He Jiankui. Courtesy of Vivian Tam (School of Biomedical Sciences, University of Hong Kong)

Robin Lovell-Badge gives his perspective on the recent report from Jiankui He of the world's first genome edited babies and discusses if and how clinical applications of germline genome editing in humans may be justifiable.


Developmental biology for agriculture

Example crop plants

In the latest Spotlight for our Advocacy series, Scott Boden and Lars Østergaard argue that technological advances in sequencing, genome editing and advanced data processing should allow developmental biologists to improve crop performance as crop yields come under pressure to meet the growing human population's needs.

Demonstrating some of these principles in a new Research Article, Laura Dixon and team analyse the flowering and growth responses of a range of wheat cultivars to warmer growth temperatures.


A new Instagram account for Development 

Our Instagram cover image, Nematostella

Our new Instagram account promotes the beauty of developmental biology through the work of our authors. Do join us there!


Workshop - New frontiers in the brain: unexpected roles of the choroid plexus-cerebrospinal fluid system in health and disease

Wiston House, where the workshop will take place

We are pleased to announce a Company of Biologist's Workshop, organised by Fiona Doetsch and Maria Lehtinen, bringing together scientists working on all aspects of choroid plexus and cerebrospinal fluid biology. The Workshop will be held in July 2019 at Wiston House, UK. Ten funded early-career places are available – apply here before 31 March 2019.

Call for papers: Chromatin and Epigenetics

Call for papers: Chromatin and Epigenetics

Development is pleased to welcome submissions for an upcoming Special Issue on ‘Chromatin and Epigenetics’, edited by Benoit Bruneau, Haruhiko Koseki, Susan Strome and Maria-Elena Torres-Padilla. This special issue aims to showcase the best research covering the chromatin-based and epigenetic mechanisms which regulate development across the plant and animal kingdoms. Submission deadline: 31 March 2019. 


PreLights – A direct and widespread role for the nuclear receptor EcR in mediating the response to ecdysone in Drosophila

PreLighter Natalie Dye

Extensive and dynamic genome binding by a steroid hormone receptor highlights the interconnection between systemic and local cues for organ development, shows a preprint written by Christopher Uyehara and Daniel McKay and highlighted by Natalie Dye.

Catch up with other recent preLights selected for the developmental biology community.


Articles of interest in our sister journals

Wnt signaling in orofacial clefts: crosstalk, pathogenesis and models
Kurt Reynolds, Priyanka Kumari, Lessly Sepulveda Rincon, Ran Gu, Yu Ji, Santosh Kumar, Chengji J. Zhou
Disease Models & Mechanisms 2019 12: dmm037051 

Loss of the deglutamylase CCP5 perturbs multiple steps of spermatogenesis and leads to male infertility
Tiziana Giordano, Sudarshan Gadadhar, Satish Bodakuntla, et al.
J Cell Sci 2019 132: jcs226951

Articles

  • Accepted manuscripts
  • Issue in progress
  • Latest complete issue
  • Issue archive
  • Archive by article type
  • Special issues
  • Subject collections
  • Sign up for alerts

About us

  • About Development
  • About the Node
  • Editors and board
  • Editor biographies
  • Travelling Fellowships
  • Grants and funding
  • Workshops and Meetings
  • The Company of Biologists

For authors

  • Submit a manuscript
  • Aims and scope
  • Presubmission enquiries
  • Article types
  • Manuscript preparation
  • Cover suggestions
  • Editorial process
  • Promoting your paper
  • Open Access
  • Biology Open transfer

Journal info

  • Journal policies
  • Rights and permissions
  • Media policies
  • Reviewer guide
  • Sign up for alerts

Contact

  • Contact Development
  • Subscriptions
  • Advertising
  • Feedback

 Twitter   YouTube   LinkedIn

© 2019   The Company of Biologists Ltd   Registered Charity 277992