News | University of California scientists recreate early development with ‘programmable embryo models,’ opening new avenues for fertility research
How a single cell becomes a complete organism in the first days after fertilization remains one of science’s greatest mysteries. Because early mammalian development takes place inside the uterus, researchers have long struggled to observe or intervene directly, limiting understanding of why embryo development sometimes fails.
A pioneering study at the University of California, Santa Cruz, is overcoming this limitation. Using advanced CRISPR technology without real embryos, researchers created self-organizing “programmable embryo models,” or embryoids, reproducing key stages of early development in the laboratory. The work was published in Cell Stem Cell.
“We want to reconstruct and even modify natural phenomena in a dish, such as embryo formation, to advance research on early developmental disorders.”
—Ali Shariati, corresponding author and assistant professor of biomolecular engineering at UC Santa Cruz
Programming stem cells with CRISPR
The study was co-led by postdoctoral researcher Gerrald Lodewijk and alumna Sayaka Kozuki, now a graduate student at Caltech, using laboratory mouse stem cells. Stem cells are like a blank canvas and can theoretically become any cell type, including brain or intestinal cells.
The team used a gentler CRISPR variant, the CRISPR activation system (CRISPRa). Rather than cutting DNA, it regulates and activates gene regions essential to embryonic development. This precise activation prompts stem cells to produce different primitive embryonic cell types.
“Instead of adding an external stimulus, we activate genetic switches the cells already possess and let them determine how to begin the journey of development,” Lodewijk explained.
More than 80% of stem cells spontaneously organized within days into structures resembling early embryos and initiated gene-expression programs closely matching natural embryos.
“The self-organization is remarkably comparable. The cells seem to know what to do; we only need to give them a gentle push.”
—Ali Shariati
Observing how early life organizes itself
The embryoid cells displayed collective behavior in culture, including rotational migration described as orderly movement like a flock of birds, ultimately forming striking early embryonic patterns.
Unlike earlier methods that used chemicals to force the production of different cell types, this study emphasized co-development, which more closely resembles natural embryonic development in the body.
“We do not make the cells individually. We let them grow together and influence one another as they would in a real embryo, recreating their biological memory as neighbors.”
—Shariati
Programmable models may reveal the causes of developmental defects
The main advantage of these embryo models is their high programmability. Researchers can study the earliest stages of life and deliberately switch genes on or off to observe which changes cause failure in cell types, tissue organization, or the entire embryo.
This provides a powerful platform for modeling developmental abnormalities without using real embryos.
The technology may eventually be extended to other species, including humans, helping scientists investigate why early human embryos often fail to implant or develop. Shariati said: “We can now see the bottlenecks at the beginning of life more clearly, which is highly significant for improving human reproductive success.”
News | University of California scientists recreate early development with ‘programmable embryo models,’ opening new avenues for fertility research
News | University of California scientists recreate early development with ‘programmable embryo models,’ opening new avenues for fertility research
How a single cell becomes a complete organism in the first days after fertilization remains one of science’s greatest mysteries. Because early mammalian development takes place inside the uterus, researchers have long struggled to observe or intervene directly, limiting understanding of why embryo development sometimes fails.
A pioneering study at the University of California, Santa Cruz, is overcoming this limitation. Using advanced CRISPR technology without real embryos, researchers created self-organizing “programmable embryo models,” or embryoids, reproducing key stages of early development in the laboratory. The work was published in Cell Stem Cell.
“We want to reconstruct and even modify natural phenomena in a dish, such as embryo formation, to advance research on early developmental disorders.”
—Ali Shariati, corresponding author and assistant professor of biomolecular engineering at UC Santa Cruz
Programming stem cells with CRISPR
The study was co-led by postdoctoral researcher Gerrald Lodewijk and alumna Sayaka Kozuki, now a graduate student at Caltech, using laboratory mouse stem cells. Stem cells are like a blank canvas and can theoretically become any cell type, including brain or intestinal cells.
The team used a gentler CRISPR variant, the CRISPR activation system (CRISPRa). Rather than cutting DNA, it regulates and activates gene regions essential to embryonic development. This precise activation prompts stem cells to produce different primitive embryonic cell types.
“Instead of adding an external stimulus, we activate genetic switches the cells already possess and let them determine how to begin the journey of development,” Lodewijk explained.
More than 80% of stem cells spontaneously organized within days into structures resembling early embryos and initiated gene-expression programs closely matching natural embryos.
“The self-organization is remarkably comparable. The cells seem to know what to do; we only need to give them a gentle push.”
—Ali Shariati
Observing how early life organizes itself
The embryoid cells displayed collective behavior in culture, including rotational migration described as orderly movement like a flock of birds, ultimately forming striking early embryonic patterns.
Unlike earlier methods that used chemicals to force the production of different cell types, this study emphasized co-development, which more closely resembles natural embryonic development in the body.
“We do not make the cells individually. We let them grow together and influence one another as they would in a real embryo, recreating their biological memory as neighbors.”
—Shariati
Programmable models may reveal the causes of developmental defects
The main advantage of these embryo models is their high programmability. Researchers can study the earliest stages of life and deliberately switch genes on or off to observe which changes cause failure in cell types, tissue organization, or the entire embryo.
This provides a powerful platform for modeling developmental abnormalities without using real embryos.
The technology may eventually be extended to other species, including humans, helping scientists investigate why early human embryos often fail to implant or develop. Shariati said: “We can now see the bottlenecks at the beginning of life more clearly, which is highly significant for improving human reproductive success.”
Source:
Collected online