Tight Junctions’ Role in Gastrulation in Human Embryos

Tight junctions between cells may play a critical role in gastrulation in human embryos. As a human embryo develops, a group of molecules guides cell multiplication and specialization, positioning them within the embryo. During gastrulation, these molecules guide embryonic stem cells to form three distinct layers, which later develop into various body parts.

Firstly, researchers at the iPS Cell Research Center in Gladstone Institutes have discovered that tight junctions between cells may have a vital role in gastrulation in human embryos.

“This study’s findings have exciting implications for designing gastrulation models and other lab techniques to differentiate stem cells into specialized cell types,” says Shinya Yamanaka, MD, PhD, a senior investigator at Gladstone and one of the study’s senior authors, which was published in the journal Developmental Cell. “A better understanding of signaling mechanisms in embryos will facilitate the replication of these processes in robust and reproducible ways.”

Transforming stem cells into human egg cells

Moreover, the team is already developing innovative techniques to transform stem cells into human egg cells for potential in vitro fertilization.

Researchers at the iPS Cell Research Center in Gladstone Institutes have therefore discovered that tight junctions between cells may have a vital role in gastrulation in human embryos.

“This study’s findings have exciting implications for designing gastrulation models and lab techniques to differentiate stem cells,” says Shinya Yamanaka, MD, PhD, a senior investigator at Gladstone and one of the study’s senior authors, published in Developmental Cell. “A better understanding of signaling mechanisms in embryos will facilitate the replication of these processes in robust and reproducible ways.”

The team uses their findings to develop innovative laboratory techniques transforming stem cells into human egg cells for potential in vitro fertilization.

Tight junctions’ critical role in gastrulation in human embryos: Discovery on the edge

While creating a gastrulation model, Vasic observed iPS cells clustering in the dish with tight junction proteins, acting as cell barriers. However, tight junctions didn’t always assemble.

Growing cells in a less-confined space allowed consistent tight junction assembly. Adding BMP4 to unconfined cells resulted in a breakthrough: only edge cells activated pathways for differentiating into various cell types.

“Tight junctions between adjacent cells seem to make them impervious to BMP4 signals,” says Vasic. “Edge cells lack a buddy for tight junctions on their outer side, making them highly responsive to BMP4 cues.”

Furthermore, CRISPR genome editing suppressed TJP1, confirming tight junctions’ significance in iPS cells. Without TJP1, all cells responded to BMP4, not just the edge cells.

“Removing tight junctions made all cells respond to BMP4,” says Yamanaka, a professor at UC San Francisco and director at the Center for iPS Cell Research and Application (CiRA), Kyoto University, Japan. “Tight junctions block cells from responding to signals, emphasizing cell structure’s role in receiving differentiation signals.”

“In summary,” says Todd McDevitt, perturbing iPS cells’ properties can alter their sensitivity to cues and change cell fate trajectory. “This principle could revolutionize iPS cells’ potential to produce homogeneous differentiated cell populations for therapeutic use.”

Creating egg cells in a dish

While creating egg cells in a laboratory setting, the research team investigated BMP4-activated cells after disrupting tight junction formation.

Excitingly, they discovered the ability to generate primordial germ cell-like cells. These lab-produced stem cells resemble the precursors of human sperm and egg cells.

So, researchers have long struggled to find a reliable method for generating primordial germ cell-like cells from iPS cells. However, Vasic and her colleagues found that suppressing TJP1 could provide a novel and efficient approach to produce these unique cells.

Inspired by these findings, Vasic established Vitra Labs, aiming to treat women’s infertility.

Vasic says, “Our goal is to generate eggs for in vitro fertilization by mimicking the natural process of egg production.” “This application adds an extra layer of significance to our study.”

Read the original article on news-medical.

Read more: Preserving Dignity: American Association for Anatomy Takes a Stand Against Exploitation of Human Body Donors.