News & Events

News & Events

Home › News & Events › 2023 › Research › Breaking down molecular barriers to shed light on pattern organization


July 21, 2023

Breaking down molecular barriers to shed light on pattern organization

Professor Shinya Yamanaka, Associate Professor Kiichiro Tomoda, and their research team at the iPS Cell Research Center at Gladstone Institute, an On-site Laboratory of Kyoto University, have shown tight junctions between cells may play a critical role in the gastrulation of human embryos.

During a process called gastrulation, pluripotent stem cells forming the tissue known as the epiblast differentiate to form the three somatic germ layers (endoderm, mesoderm, and ectoderm). Spatial organization and axis formation are critical during this early embryonic developmental period, with which the extracellular signaling molecule BMP4 has been known for many years to be critically involved.

In this study, the research team found that tight junctions--a type of intercellular adhesion complexes--specify sensitivity toward BMP4 in an iPS cell-derived differentiation model using that recapitulates the process of gastrulation of human embryos. They identified TJP1 as a critical factor that helps set up the molecular barrier defining the apical and basolateral polarity of the cells in the early embryo. Notably, they observed TJP1 knockdown results in ubiquitous and sustained activation of intracellular signaling pathways downstream of BMP4 and ushers the genetically modified pluripotent stem cell colonies toward a cell fate known as primordial germ cell-like cell (PGCLC), which are precursors of human sperm and egg cells. Thus, by illuminating the molecular details of how tight junctions created with TJP1 affect BMP4 signaling, the researchers have discovered a novel way to effectively produce PGCLCs that may be used one day to generate eggs for in vitro fertilization to help treat female infertility.

The results of this research are featured in a news article from the Gladstone Institutes.

The results of this study were published in Developmental Cell on June 23, 2023.

Paper Details
  • Journal: Developmental Cell
  • Title: Loss of TJP1 disrupts gastrulation patterning and increases differentiation toward the germ cell lineage in human pluripotent stem cells
  • Authors: Ivana Vasic1,2, Ashley R.G. Libby1,3, Annie Maslan2,4,5, Emily A. Bulger1,3, David Zalazar1,
    Martina Z. Krakora Compagno1, Aaron Streets2,4,5,6, Kiichiro Tomoda1,7, Shinya Yamanaka1,7*,
    Todd C. McDevitt1,8*
    *: Corresponding authors
  • Author Affiliations:
    1. Gladstone Institute of Cardiovascular Disease, Gladstone Institutes
    2. UC Berkeley-UC San Francisco Graduate Program in Bioengineering, University of California
    3. Developmental and Stem Cell Biology Ph.D. Program, University of California
    4. Department of Bioengineering, University of California
    5. Center for Computational Biology, University of California
    6. Chan Zuckerberg Biohub
    7. Center for iPS Cell Research and Application, Kyoto University
    8. Department of Bioengineering and Therapeutic Sciences, University of California
go top