Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
GATA6 suppression enhances lung specification from human pluripotent stem cells
Chia-Min Liao, … , Deborah L. French, Paul Gadue
Chia-Min Liao, … , Deborah L. French, Paul Gadue
Published June 11, 2018
Citation Information: J Clin Invest. 2018;128(7):2944-2950. https://doi.org/10.1172/JCI96539.
View: Text | PDF
Concise Communication Development Pulmonology

GATA6 suppression enhances lung specification from human pluripotent stem cells

  • Text
  • PDF
Abstract

The transcription factor GATA6 has been shown to be important for lung development and branching morphogenesis in mouse models, but its role in human lung development is largely unknown. Here, we studied the role of GATA6 during lung differentiation using human pluripotent stem cells. We found that the human stem cell lines most efficient at generating NKX2.1+ lung progenitors express lower endogenous levels of GATA6 during endoderm patterning and that knockdown of GATA6 during endoderm patterning increased the generation of these cells. Complete ablation of GATA6 resulted in the generation of lung progenitors displaying increased cell proliferation with up to a 15-fold expansion compared with control cells, whereas the null cell line displayed a defect in further development into mature lung cell types. Furthermore, transgenic expression of GATA6 at the endoderm anteriorization stage skewed development toward a liver fate at the expense of lung progenitors. Our results suggest a critical dosage effect of GATA6 during human endoderm patterning and a later requirement during terminal lung differentiation. These studies offer an approach of modulating GATA6 expression to enhance the production of lung progenitors from human stem cell sources.

Authors

Chia-Min Liao, Somdutta Mukherjee, Amita Tiyaboonchai, Jean Ann Maguire, Fabian L. Cardenas-Diaz, Deborah L. French, Paul Gadue

×

Figure 1

Low GATA6 expression during endoderm patterning enhances lung progenitor generation.

Options: View larger image (or click on image) Download as PowerPoint
Low GATA6 expression during endoderm patterning enhances lung progenitor...
(A) Schematic of the lung differentiation protocol. (B and C) The expression of NKX2.1+ in lung progenitors (B) and GATA6 at anteriorization (C) from 3 human PSC lines (n = 7). (D) Linear regression analysis of GATA6 on day 7 versus NKX2.1 on day 13 from 6 WT human cell lines. (E and F) Transfection of 2 siRNAs against GATA6 (G6-A and G6-B) or control scrambled siRNA (Ctrl) at anteriorization stage in MEL1 ESCs. GATA6 expression (E) and quantification (F) after siRNA treatment (n = 4). (G) The expression of NKX2.1 in cells treated with GATA6 siRNAs. (H) Average expression and absolute cell number of NKX2.1+ cells (n = 5). (I) Coexpression of indicated populations treated with GATA6 siRNAs (n = 5). (J) SOX2 and NKX2.1 expression of cells treated with GATA6 siRNAs (n = 5). (K) Coexpression of NKX2.1 and Ki67 in cells treated with GATA6 siRNAs (n = 5). Data indicate the mean ± SEM. *P < 0.05, **P < 0.01 by 2-tailed t test.
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts