Skip to main content

Main menu

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Subject Collections
    • JASN Podcasts
    • Archives
    • Saved Searches
    • ASN Meeting Abstracts
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Subscriptions
  • More
    • About JASN
    • Alerts
    • Advertising
    • Editorial Fellowship Program
    • Feedback
    • Reprints
    • Impact Factor
  • ASN Kidney News
  • Other
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology

User menu

  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
American Society of Nephrology
  • Other
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Advertisement
American Society of Nephrology

Advanced Search

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Subject Collections
    • JASN Podcasts
    • Archives
    • Saved Searches
    • ASN Meeting Abstracts
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Subscriptions
  • More
    • About JASN
    • Alerts
    • Advertising
    • Editorial Fellowship Program
    • Feedback
    • Reprints
    • Impact Factor
  • ASN Kidney News
  • Follow JASN on Twitter
  • Visit ASN on Facebook
  • Follow JASN on RSS
  • Community Forum
Basic Research
You have accessRestricted Access

Rapid and Efficient Differentiation of Human Pluripotent Stem Cells into Intermediate Mesoderm That Forms Tubules Expressing Kidney Proximal Tubular Markers

Albert Q. Lam, Benjamin S. Freedman, Ryuji Morizane, Paul H. Lerou, M. Todd Valerius and Joseph V. Bonventre
JASN June 2014, 25 (6) 1211-1225; DOI: https://doi.org/10.1681/ASN.2013080831
Albert Q. Lam
*Renal Division, Department of Medicine, and
†Harvard Stem Cell Institute, Cambridge, Massachusetts; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Benjamin S. Freedman
*Renal Division, Department of Medicine, and
†Harvard Stem Cell Institute, Cambridge, Massachusetts; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ryuji Morizane
*Renal Division, Department of Medicine, and
‡Internal Medicine, Keio University School of Medicine, Tokyo, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul H. Lerou
†Harvard Stem Cell Institute, Cambridge, Massachusetts; and
§Department of Newborn Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. Todd Valerius
*Renal Division, Department of Medicine, and
†Harvard Stem Cell Institute, Cambridge, Massachusetts; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joseph V. Bonventre
*Renal Division, Department of Medicine, and
†Harvard Stem Cell Institute, Cambridge, Massachusetts; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data Supps
  • Info & Metrics
  • View PDF
Loading

Abstract

Human pluripotent stem cells (hPSCs) can generate a diversity of cell types, but few methods have been developed to derive cells of the kidney lineage. Here, we report a highly efficient system for differentiating human embryonic stem cells and induced pluripotent stem cells (referred to collectively as hPSCs) into cells expressing markers of the intermediate mesoderm (IM) that subsequently form tubule-like structures. Treatment of hPSCs with the glycogen synthase kinase-3β inhibitor CHIR99021 induced BRACHYURY+MIXL1+ mesendoderm differentiation with nearly 100% efficiency. In the absence of additional exogenous factors, CHIR99021-induced mesendodermal cells preferentially differentiated into cells expressing markers of lateral plate mesoderm with minimal IM differentiation. However, the sequential treatment of hPSCs with CHIR99021 followed by fibroblast growth factor-2 and retinoic acid generated PAX2+LHX1+ cells with 70%–80% efficiency after 3 days of differentiation. Upon growth factor withdrawal, these PAX2+LHX1+ cells gave rise to apically ciliated tubular structures that coexpressed the proximal tubule markers Lotus tetragonolobus lectin, N-cadherin, and kidney-specific protein and partially integrated into embryonic kidney explant cultures. With the addition of FGF9 and activin, PAX2+LHX1+ cells specifically differentiated into cells expressing SIX2, SALL1, and WT1, markers of cap mesenchyme nephron progenitor cells. Our findings demonstrate the effective role of fibroblast growth factor signaling in inducing IM differentiation in hPSCs and establish the most rapid and efficient system whereby hPSCs can be differentiated into cells with features characteristic of kidney lineage cells.

  • Copyright © 2014 by the American Society of Nephrology
View Full Text
PreviousNext
Back to top

In this issue

Journal of the American Society of Nephrology: 25 (6)
Journal of the American Society of Nephrology
Vol. 25, Issue 6
June 2014
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
View Selected Citations (0)
Print
Download PDF
Sign up for Alerts
Email Article
Thank you for your help in sharing the high-quality science in JASN.
Enter multiple addresses on separate lines or separate them with commas.
Rapid and Efficient Differentiation of Human Pluripotent Stem Cells into Intermediate Mesoderm That Forms Tubules Expressing Kidney Proximal Tubular Markers
(Your Name) has sent you a message from American Society of Nephrology
(Your Name) thought you would like to see the American Society of Nephrology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Rapid and Efficient Differentiation of Human Pluripotent Stem Cells into Intermediate Mesoderm That Forms Tubules Expressing Kidney Proximal Tubular Markers
Albert Q. Lam, Benjamin S. Freedman, Ryuji Morizane, Paul H. Lerou, M. Todd Valerius, Joseph V. Bonventre
JASN Jun 2014, 25 (6) 1211-1225; DOI: 10.1681/ASN.2013080831

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Rapid and Efficient Differentiation of Human Pluripotent Stem Cells into Intermediate Mesoderm That Forms Tubules Expressing Kidney Proximal Tubular Markers
Albert Q. Lam, Benjamin S. Freedman, Ryuji Morizane, Paul H. Lerou, M. Todd Valerius, Joseph V. Bonventre
JASN Jun 2014, 25 (6) 1211-1225; DOI: 10.1681/ASN.2013080831
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Abstract
    • Results
    • Discussion
    • Concise Methods
    • Disclosures
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data Supps
  • Info & Metrics
  • View PDF

More in this TOC Section

  • NBCn1 Increases NH4+ Reabsorption Across Thick Ascending Limbs, the Capacity for Urinary NH4+ Excretion, and Early Recovery from Metabolic Acidosis
  • Adverse Maternal and Fetal Outcomes in a Novel Experimental Model of Pregnancy after Recovery from Renal Ischemia-Reperfusion Injury
  • TrkC Is Essential for Nephron Function and Trans-Activates Igf1R Signaling
Show more Basic Research

Cited By...

  • High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human embryonic stem cell gastruloid cultures
  • Emerging Kidney Models to Investigate Metabolism, Transport, and Toxicity of Drugs and Xenobiotics
  • Identification of direct negative cross-talk between the SLIT2 and bone morphogenetic protein-Gremlin signaling pathways
  • Directed differentiation of human pluripotent stem cells to blood-brain barrier endothelial cells
  • (Re)Building a Kidney
  • Does Renal Repair Recapitulate Kidney Development?
  • Human Induced Pluripotent Stem Cell-Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation
  • The origin of the mammalian kidney: implications for recreating the kidney in vitro
  • Google Scholar

Similar Articles

Related Articles

  • PubMed
  • Google Scholar

Articles

  • Current Issue
  • Early Access
  • Subject Collections
  • Article Archive
  • ASN Annual Meeting Abstracts

Information for Authors

  • Submit a Manuscript
  • Author Resources
  • Editorial Fellowship Program
  • ASN Journal Policies
  • Reuse/Reprint Policy

About

  • JASN
  • ASN
  • ASN Journals
  • ASN Kidney News

Journal Information

  • About JASN
  • JASN Email Alerts
  • JASN Key Impact Information
  • JASN Podcasts
  • JASN RSS Feeds
  • Editorial Board

More Information

  • Advertise
  • ASN Podcasts
  • ASN Publications
  • Become an ASN Member
  • Feedback
  • Follow on Twitter
  • Password/Email Address Changes
  • Subscribe

© 2021 American Society of Nephrology

Print ISSN - 1046-6673 Online ISSN - 1533-3450

Powered by HighWire