Behind the Paper

The Second Domestication of Cows: Reprogramming Stem Cells for the Future of Meat

What if we could domesticate cow cells like we once domesticated cows? Using CRISPR screening, we identified genes that limit bovine stem cell growth and found ways to boost yields by up to 50%. This 'second domestication' could bring scalable, affordable cultured meat closer to reality.

If there’s one thing humans are remarkably good at, it’s adapting. When we can’t adapt ourselves, we adapt everything around us - plants, animals, even entire ecosystems - to fit our needs. Over thousands of years, we’ve reshaped the natural world: sweeter watermelons, seedless bananas, faster-growing chickens, cows with more muscle and less aggression. Domestication is one of humanity’s oldest survival tools.

But the world is changing faster than ever. As the global population approaches 10 billion, our traditional food systems are under enormous strain. Producing meat, in particular, demands vast amounts of land, water, and energy - and it contributes significantly to greenhouse gas emissions, biodiversity loss, antibiotic resistance, and even the risk of zoonotic diseases. Simply put, the way we’ve always produced meat won’t scale into the future.

That’s where cultured meat - also called cellular agriculture - comes in. Instead of raising and slaughtering animals, we can grow real animal cells directly in controlled environments. In theory, this approach could drastically reduce environmental impact, improve food security, and remove many ethical concerns. But there’s a big problem: the cells we rely on, especially bovine mesenchymal stem cells (bMSCs) - the workhorses behind most cultured beef efforts - don’t grow fast enough.

The Problem with Slow Cells

Cultured meat production depends on stem cells’ ability to both proliferate (make more of themselves) and differentiate into specialized tissues like muscle and fat. In principle, one tiny sample of cells could eventually produce kilograms of edible meat. But reality isn’t so simple.

Bovine MSCs, like most stem cells, hit two major roadblocks:

  1. Slow growth rates - compared to embryonic or induced pluripotent stem cells, they divide slower.

  2. Replicative senescence - after a certain number of divisions, cells enter a “retirement mode,” where they stop dividing entirely.

These biological limitations are a bottleneck for scalability and affordability. Even a modest boost in cell proliferation, when compounded over dozens of cell divisions, could result in orders of magnitude more meat for the same investment of time, energy, and resources.

So we asked ourselves a simple question: what if we could “domesticate” cow stem cells the same way ancient humans domesticated cows themselves?

The Second Domestication of Cows

Thousands of years ago, humans domesticated cattle by selecting animals with traits that made them more useful to us - faster growth, better temperament, higher yields. But cultured meat doesn’t care if a cow is aggressive, horned, or adapted to a particular climate. On a petri dish, we care about completely different traits:

  • Faster cell division

  • Resistance to senescence

  • Predictable yields

In other words, we need to domesticate the cells themselves.

Our recent paper, Pooled CRISPR Screens Identify Key Regulators of Bovine Stem Cell Expansion for Cultured Meat explores exactly this idea. Using CRISPR-based screening, we tested hundreds of genes to find those that naturally limit MSC proliferation - and asked what happens if we remove those “brakes.”

CRISPR Meets Cultured Meat

We designed a targeted CRISPR knockout screen - essentially, we gave thousands of bMSCs slightly different “genetic edits” and let them compete. If knocking out a gene helped a cell grow faster, those edited cells would gradually take over the population.

This approach let us study nearly 600 genes known to influence cell growth, stemness, or differentiation. Among the many candidates, two genes stood out immediately: TP53 and PTEN.

Knocking out these genes had a dramatic effect:

  • Up to 50% faster proliferation rates

  • Extended “youthfulness” of the cells - they kept dividing long after normal cells stopped

  • More total cell doublings overall, meaning significantly higher yields

The strategy worked like a form of almost-directed evolution: instead of manually picking winners, we set up an environment where the “fittest” edits naturally emerged over time.

TP53 and PTEN

Interestingly, both TP53 and PTEN are well-known genes in cancer biology - they act as tumor suppressors in normal tissues, helping keep cell growth in check. Removing them effectively “releases the brakes,” which explains why we saw such strong effects on MSC expansion.

While these knockouts made cells grow faster, they also slightly reduced the cells’ ability to differentiate - especially into adipocytes (fat cells) and, in some cases, muscle cells. For cultured meat, where both fat and muscle are crucial for texture and flavor, this introduces a design challenge: how do we balance speed and quality?

This is part of the beauty of the CRISPR-screening approach. Now that we know which pathways influence growth, we can think more creatively:

  • Combine edits to get the best of both worlds

  • Use temporary modulation of these genes during expansion, then restore normal function for differentiation

  • Explore entirely new gene targets linked to metabolism, stemness, and lineage control

More Than Just Two Genes

While TP53 and PTEN were our headline discoveries, the screen revealed other interesting pathways that could be harnessed for cultured meat. For example, genes related to chondrogenesis - the process of forming cartilage - appeared to act as subtle growth brakes. Inhibiting these pathways boosted MSC expansion while potentially steering cells away from unwanted cartilage formation.

We also uncovered roles for metabolic regulators, like components of the mitochondrial pyruvate carrier, which seem to shift MSCs into a more “energy-efficient” growth mode. These findings open the door to optimizing cultured meat production at multiple biological levels, from energy metabolism to cell cycle control.

Why This Matters

Cultured meat isn’t just a technological curiosity - it’s part of a larger movement to reimagine how we produce food in a warming, crowded, and resource-constrained world. But for cultured meat to make a meaningful impact, we need breakthroughs like this one: ways to grow more cells, faster, at lower cost.

Our work doesn’t solve every challenge - scaling bioreactors, reducing serum dependency, ensuring safety, and navigating regulatory frameworks are all ahead of us - but it does give us a roadmap for improving one of the biggest bottlenecks: the cells themselves.

In a sense, this is the second domestication of cows. Not by reshaping the animals, but by reprogramming the biology of their cells to meet the needs of the future.

Looking Ahead

We envision a future where cultured meat production becomes scalable, affordable, and diverse - where cells are optimized for specific cuts, textures, and flavors, just as ancient breeders once optimized livestock for size or temperament.

The CRISPR screening approach we developed can easily be extended beyond bovine MSCs to other cell types critical for cultured meat, like satellite cells for muscle, induced pluripotent stem cells, or fat-optimized lines. It’s a platform for systematic cell engineering - and we’ve only scratched the surface.

The challenges ahead are real, but so are the opportunities. Cultured meat is a chance to rethink meat from the ground up - and maybe, with the right tools, we’ll finally be able to grow the future of food.