April 15, 2025
U荔枝视频 research shows pig and human genes have closer relationship than previously thought
Research led by at the 荔枝视频 Faculty of Veterinary Medicine is uncovering how species-specific developmental timing shapes early development, using pig stem-cells.
Understanding how cells grow and change can unlock new therapies for regenerative medicine and Chu鈥檚 team is showing encouraging results by creating retinal tissues similar to that found in human eyes.
Last year, the team鈥檚 work, published in , focused on porcine induced pluripotent stem cells (PiPSCs). These are pig cells reprogrammed into an embryonic-like state that can become any cell type in the body.
An undifferentiated pig pluripotent stem cell colony shows the presence of genes that help the cells stay in their stem cell state.
J. Vanessa Conrad, Chu Lab
In the first study, Chu鈥檚 lab developed a transgene-free method to create PiPSCs safely, without permanently altering their DNA. These cells retained their natural developmental 鈥渃locks鈥 in the lab, mirroring pigs鈥 in vivo (in a living organism) timing. This allowed the team to model a process called the segmentation clock鈥攁 rhythmic cycle that controls how embryos form body segments. In pigs, this cycle ticks every 3.7 hours, placing them between the fast-paced mouse clock (~2 hours) and the slower human clock (~5 hours).
鈥淧ig stem cells preserve their species-specific pace, even outside the body,鈥 says Dr. Chu. 鈥淭hat鈥檚 incredibly useful for studying how timing affects development.鈥
From timing to tissues: building the pig retina
In a published this month, in collaboration with Dr. David Gamm at the University of Wisconsin鈥揗adison, the team used PiPSCs to grow retinal organoids鈥3D retina-like tissues containing light-sensitive photoreceptors.
However, the process wasn鈥檛 straightforward. When the team applied standard human retinal differentiation protocols, the pig cells rarely formed retinal structures. The issue? The human protocol didn鈥檛 match pigs鈥 faster developmental timing or pace.
By shortening the timeline and fine-tuning molecular cues to reflect porcine development, the researchers developed a robust, reproducible method that generated hundreds of retinal organoids per experiment鈥攁 major leap forward. The organoids contained organized layers of rods, cones, bipolar cells, and M眉ller glia (cells of the retina), with structural features essential for sensing light.
On day 40 of differentiation, pig stem cell-derived three-dimensional retinal organoids contained retinal ganglion cells (SNCG+ in green) and early photoreceptors (RCVRN+, in red). The cell nuclei are stained blue.
Kimberly L. Edwards, Gamm Lab (UW-Madison)
Importantly, these pig retinal tissues showed gene expression profiles remarkably similar to human retinal organoids, especially in photoreceptors, suggesting pigs can serve as a valuable model for testing cell-based therapies.
These findings have broad implications for regenerative medicine, veterinary science, and translational research. They highlight the value of pigs as a bridge species鈥攂iologically closer to humans than rodents; for modeling development and testing therapies.
鈥淭his is about more than pigs,鈥 says Dr. Chu. 鈥淚t鈥檚 about finding the right models to understand how time shapes development鈥攁nd how we can use that to repair or replace tissues.鈥
As the team continues cross-species comparisons, they also aim to uncover how mistimed development may underlie congenital conditions, and how stem cell technologies can help correct it.