News | How Cell Structure Affects Embryonic Development: The Role of Tight Junctions
During human embryonic development, molecular signals direct cells to divide and differentiate, ultimately determining their position and identity in the embryo. Gastrulation is a foundational step in which a single layer of embryonic stem cells differentiates into three distinct cell layers that form the basis of future body structures.
Recent research suggests that tight junctions between cells may play a vital role in this process. Researchers at the Gladstone Institutes' iPS Cell Research Center found that tight junctions are critical during human embryonic gastrulation, offering new insight for stem-cell research and the design of related experimental models.
Gastrulation and the research breakthrough
During gastrulation, embryonic stem cells differentiate into three layers of embryonic tissue. Studying this process has become important in regenerative medicine. Scientists often model it with induced pluripotent stem (iPS) cells, which are converted from adult cells and can differentiate into any somatic cell type.
When studying gastrulation with iPS cells, scientists found that cells responded differently even though all were stimulated by BMP4, a key signaling molecule. Why only some cells differentiate into distinct cell types despite receiving the same BMP4 signal remained unclear.
Lead researcher Dr. Ivana Vasic observed that iPS cells clustered in culture dishes and formed tight junctions, barriers thought to prevent signaling molecules from passing between cells. She also found that these junctions did not always assemble properly.
How tight junctions affect gastrulation
Further experiments showed that tight junctions assembled normally when cells were cultured in a less confined space. After BMP4 was added, only cells at the edge of the cluster received enough of the signal to initiate differentiation.
Dr. Vasic said, "Tight junctions between cells seem to prevent them from responding to BMP4 signals, but edge cells do not form tight junctions with other cells, allowing them to receive the strongest BMP4 signal."
To confirm the importance of tight junctions in gastrulation, researchers used CRISPR gene editing to suppress production of TJP1, a key tight-junction protein. Without TJP1, every cell responded to BMP4, not only edge cells.
Professor Yamanaka explained, "Our experiments showed that removing tight junctions allowed all cells to respond to BMP4. This indicates that tight junctions shield signals in the gastrulation model and that cell structure is crucial to how differentiation signals are received."
New progress in germ-cell research
The team also found that suppressing TJP1 not only produced a BMP4 response but also generated primordial germ cell-like cells. Derived from iPS cells, they resemble human sperm and egg precursor cells in form and function.
Dr. Vasic said, "Suppressing TJP1 gave us a new way to efficiently produce these unique germ cells, which may offer new approaches to treating female infertility."
Potential applications
The team hopes these findings will improve stem-cell conversion techniques, especially for generating human oocytes. Dr. Vasic has founded Vitra Labs to apply this method to female infertility treatment, particularly the generation of oocytes for in vitro fertilization.
She added, "We are trying to recreate the biology of egg formation and hope this method can generate eggs for use in IVF."
News | How Cell Structure Affects Embryonic Development: The Role of Tight Junctions
News | How Cell Structure Affects Embryonic Development: The Role of Tight Junctions
During human embryonic development, molecular signals direct cells to divide and differentiate, ultimately determining their position and identity in the embryo. Gastrulation is a foundational step in which a single layer of embryonic stem cells differentiates into three distinct cell layers that form the basis of future body structures.
Recent research suggests that tight junctions between cells may play a vital role in this process. Researchers at the Gladstone Institutes' iPS Cell Research Center found that tight junctions are critical during human embryonic gastrulation, offering new insight for stem-cell research and the design of related experimental models.
Gastrulation and the research breakthrough
During gastrulation, embryonic stem cells differentiate into three layers of embryonic tissue. Studying this process has become important in regenerative medicine. Scientists often model it with induced pluripotent stem (iPS) cells, which are converted from adult cells and can differentiate into any somatic cell type.
When studying gastrulation with iPS cells, scientists found that cells responded differently even though all were stimulated by BMP4, a key signaling molecule. Why only some cells differentiate into distinct cell types despite receiving the same BMP4 signal remained unclear.
Lead researcher Dr. Ivana Vasic observed that iPS cells clustered in culture dishes and formed tight junctions, barriers thought to prevent signaling molecules from passing between cells. She also found that these junctions did not always assemble properly.
How tight junctions affect gastrulation
Further experiments showed that tight junctions assembled normally when cells were cultured in a less confined space. After BMP4 was added, only cells at the edge of the cluster received enough of the signal to initiate differentiation.
Dr. Vasic said, "Tight junctions between cells seem to prevent them from responding to BMP4 signals, but edge cells do not form tight junctions with other cells, allowing them to receive the strongest BMP4 signal."
To confirm the importance of tight junctions in gastrulation, researchers used CRISPR gene editing to suppress production of TJP1, a key tight-junction protein. Without TJP1, every cell responded to BMP4, not only edge cells.
Professor Yamanaka explained, "Our experiments showed that removing tight junctions allowed all cells to respond to BMP4. This indicates that tight junctions shield signals in the gastrulation model and that cell structure is crucial to how differentiation signals are received."
New progress in germ-cell research
The team also found that suppressing TJP1 not only produced a BMP4 response but also generated primordial germ cell-like cells. Derived from iPS cells, they resemble human sperm and egg precursor cells in form and function.
Dr. Vasic said, "Suppressing TJP1 gave us a new way to efficiently produce these unique germ cells, which may offer new approaches to treating female infertility."
Potential applications
The team hopes these findings will improve stem-cell conversion techniques, especially for generating human oocytes. Dr. Vasic has founded Vitra Labs to apply this method to female infertility treatment, particularly the generation of oocytes for in vitro fertilization.
She added, "We are trying to recreate the biology of egg formation and hope this method can generate eggs for use in IVF."
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Collected online