Living mouse created with stem cells that predate animals

The great evolutionary leap from unicellular organisms to the animal kingdom took place roughly 700 million years ago. A new breakthrough offers a glimpse into the molecular tools that may have enabled this colossal shift.

Scientists have just made a breakthrough achievement by successfully creating mouse stem cells from the genes of a single-celled life form.

Converting stem cells into a live mouse

The feat is remarkable because stem cells have the unique ability to both self-replicate and transform into other cells with different functions.

The study reveals how scientists used lab-produced stem cells to form a living, breathing mouse from a developing embryo.

Perhaps what is even more surprising is that the genes facilitating this stem cell division and specialization were previously believed to be confined only within animals and not present in single-celled protists from a billion years ago.

“The molecular tool kit of stem cells is much older than we thought previously. These molecular tools are older than animal stem cells themselves,” noted Ralf Jauch, a study author and a renowned stem cell biologist at the University of Hong Kong.

This newfound understanding of natural evolution could pave the way for improved stem cell models and potentially combat diseases and aging.

Animals and protists: What’s the difference?

The difference between animals and protists goes beyond the number of cells. Protists, usually unicellular microscopic organisms that are not classified as animals, fungi, or plants, perform all functions within a single cell.

Meanwhile, animals are like master delegators, assigning cells to specific tasks, while other cells take care of different actions.

“We know that animals, most of them have stem cells because it’s something that you need. You need cells that can divide but at the same time give rise to other cells,” explained Alex de Mendoza, a study author from Queen Mary University of London.

The Yamanaka factors

A fascinating discovery in 2012 by stem cell researcher Shinya Yamanaka revolutionized our understanding of stem cells. He found that adult cells could be transformed into stem cells by introducing four specific genes (Sox2, Pou5F1, Klf4, and Myc), coined as the Yamanaka factors.

This capability was initially considered exclusive to the animal kingdom since it seemed unnecessary in a unicellular organism.

However, de Mendoza and his colleagues recently discovered a few Yamanaka factors in the genomes of protists, challenging this belief.

Creating mouse cells from ancient genes

The team located these genes in a protist about the size of a dust particle named a choanoflagellate. They replaced a Sox2 gene from a mouse with the similar gene found in the choanoflagellates, successfully reprogramming the cells to a stem cell state.

The mouse developed with characteristics from both its original embryo and the lab-induced stem cells.

However, not all the experiments succeeded. The introduction of the Pou gene, found in the choanoflagellate, to mouse cells, didn’t induce stem cells.

This suggested that the Pou gene might have required more evolutionary modifications before it achieved its function in modern animals.

Reprogramming of mouse cells

The successful reprogramming of mouse cells to a stem cell state through the introduction of a similar gene found in the choanoflagellates raises intriguing questions about the underlying mechanisms at play.

The researchers will not explore deeper to understand how these genetic factors interact with cellular processes to reprogram and transform cell identity.

By unraveling these intricate mechanisms, scientists aim to gain further insights into the potential applications of gene reprogramming in various fields, including regenerative medicine and developmental biology.

Implications for evolutionary biology

The discoveries made through this study on mouse stem cells have broad implications for both evolutionary biology and medical research.

By examining the shared genetic features between choanoflagellates and multicellular organisms, scientists can gain valuable knowledge about the evolutionary origins of complex traits and functions.

Understanding the ancient genetic toolkit employed by our ancestors can shed light on the development and diversification of life on Earth.

Furthermore, these findings have the potential to inform advancements in medical research, offering new avenues for studying cellular reprogramming and potentially unlocking novel therapeutic strategies for various diseases and conditions.

The synergistic combination of evolutionary insights and biomedical applications holds great promise for scientific innovation and improving human health.

Ancient coding for a modern world

De Mendoza suggests that choanoflagellates and our ancient ancestors may have used these gene capabilities to regulate basic functions, like cell proliferation. However, multicellular animals could have repurposed them to build complex bodies.

“Evolution doesn’t always need to invent. Usually, you use whatever you have, and then you build something new from mostly recycled parts,” noted de Mendoza.

This research on mouse stem cells highlights the marvels of evolution and the intricate characteristics of our ancestors. It also demonstrates the power of human ingenuity, transforming genetic relics from the past into tools for scientific advancements today.

The study is published in the journal Nature Communications.

Image Credit: Gao Ya and Alvin Kin Shing Lee, with thanks to the Centre for Comparative Medicine Research (CCMR) for their support

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