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TET Proteins: The Cell's Guiding Stars

Discover how TET proteins shape cell development and gene behavior.

Raphaël Pantier, Elisa Barbieri, Sara Gonzalez Brito, Ella Thomson, Tülin Tatar, Douglas Colby, Man Zhang, Ian Chambers

― 7 min read


TET Proteins: Cell Fate TET Proteins: Cell Fate Controllers proteins in gene regulation. Explore the essential roles of TET
Table of Contents

TET proteins are special tools in our cells that help control how genes are turned on and off. They are like a set of helpful guides that make sure everything works just right, especially when it comes to how our cells develop and function. When TET proteins are working properly, they help keep our DNA clean and tidy by removing excess markers that might confuse the cell about what to do.

What Are TET Proteins?

TET stands for Ten-Eleven Translocation. These proteins are found in many living things, including humans. There are three TET proteins known as TET1, TET2, and TET3. These proteins share a similar design, which means they have evolved over time to serve important functions in our cells.

The Big Job of TET Proteins

The main job of TET proteins is to take care of a process called DNA demethylation. This is like cleaning up a messy room; they remove unwanted items (methyl groups) attached to our DNA that can stop genes from doing their jobs. When TET proteins do their job well, they help cells grow and develop properly.

TET Proteins and Development

During early development, TET proteins are very active. They help guide Stem Cells, which are like blank slates, on how to become different types of cells in the body. Just imagine a group of kids in a playground, each trying to figure out what game to play. TET proteins help them decide if they want to be muscle cells, nerve cells, or any other type of cell.

What Happens When TET Proteins Don’t Work?

If TET proteins are missing or broken, it can cause a lot of confusion in the cells. For instance, if TET1 is not working, it can mess up how eggs develop and how the baby grows later on. With TET2, there might be issues related to blood cells, leading to health problems. TET3 is also important, and if it's missing, it can lead to serious issues right after birth.

The Importance of TET Proteins in Stem Cells

When scientists looked at stem cells without TET proteins, they discovered that these cells struggled to change into other types of cells. They wanted to remain as stem cells, like kids who just want to play on the swings without trying any other games.

The Special Technique: CRISPR/Cas9

To better understand TET proteins, researchers used a clever trick called CRISPR/Cas9. This is like having a pair of scissors for DNA. With this method, they could cut out the parts of the DNA that make TET proteins, allowing them to study what happens when TET proteins are missing.

Observing TET Knockout Cells

When scientists created cells that completely lacked TET proteins, they noticed something interesting. These cells could still change into a special type of cell called EpiLCs, which are important in development. However, they really struggled to become other types of cells needed to form organs and tissues.

TET Proteins and the Somatic vs. Germline Fate

One fascinating discovery was how TET proteins help the cells decide between two paths: becoming regular body (somatic) cells or special germline cells, which are responsible for making eggs and sperm. When TET proteins were missing, the cells were much more likely to choose the germline path.

Think of it like a school play where kids can choose to act as pirates or princesses. TET proteins help the kids decide whether they want to be a pirate or a princess. But without these proteins, everyone suddenly wants to be a pirate!

Avoiding the Somatic Trap

Interestingly, when TET proteins were absent, cells started to take on germline characteristics much faster than normal. This means they were able to become cells that could eventually form eggs or sperm, even when they shouldn't have been. It’s like kids at a birthday party who want to join a game before they’ve even finished their cake.

Time for a Change: Transitioning States

The research also showed that cells lacking TET proteins could move between different states of being. They could switch from naïve cells (just starting out) to more specialized cells without difficulty. This suggests TET proteins don’t have a big say in this transition; it’s like getting on a bus that takes you wherever you want to go, regardless of whether or not the driver is paying attention.

Self-Renewal and TET Proteins

In the lab, scientists found that cells without TET proteins could still grow and fill a dish, but they didn’t change into other types of cells as they should. These TET-deficient cells were like kids who could eat all the candy but refused to share or join any games. They thrived as cells but didn’t want to transform into something new.

TET Proteins and Cell Behavior

When scientists looked at how these cells behaved, they noticed that TET-deficient cells were still able to express important genes involved in development. It’s like kids who may not want to play games but can still impress their friends with their math skills. They just won’t participate in the fun!

The Germline Commitment Discovery

As scientists dug deeper into the roles of TET proteins, they learned that TET-deficient cells could still express germline markers. This means that while TET proteins are often seen as helpful in managing cell fate, their absence drives cells toward being germline cells more quickly than expected.

Time to Shine: TET-DKO and TET-TKO Lines

Researchers looked at different combinations of TET proteins. In some experiments, they knocked out just one protein or two, resulting in TET-deficient cells that still managed to express markers typical of germline cells. It’s like taking away the chocolate from a recipe but still having a great dessert – unexpected but surprisingly effective!

TET Proteins as Gatekeepers

All this information leads to a big idea: TET proteins act as gatekeepers. They don't just help cells figure out what to do; they also keep the pathways to germline and somatic fates distinct. If these proteins go missing, the lines start to blur, and cells might take paths they shouldn’t be taking.

Conclusion: The Future of TET Research

As scientists continue to discover more about TET proteins, they could help us learn about not only cell development but also how diseases might arise when these proteins don’t work the way they should. Whether or not TET proteins are like the good teachers in the school of cell development is still a matter of study, but one thing's for sure: they help keep the class in order.

Fun With TETs

To sum it all up, TET proteins are like the guides at a fun amusement park. They help all the rides run smoothly and make sure no one gets lost! When they are around, you know it's going to be a good time. But without them? Well, let’s just say it’s a wild ride that could lead to unexpected twists and turns.

In future studies, who knows? We might just find out more about the whys and hows of TET proteins, just like discovering a secret passageway in a theme park that leads to the best rides. And as we unravel the mysteries of TET proteins, we get closer to understanding the very building blocks of life itself!

Original Source

Title: TET knockout cells transit between pluripotent states and exhibit precocious germline entry

Abstract: TET1, TET2 and TET3 are DNA demethylases with critical roles in development and differentiation. To assess the contributions of TET proteins to cell function during early development, single and compound knockouts of Tet genes in mouse pluripotent embryonic stem cells (ESCs) were generated. Here we show that TET proteins are not required to transit between naive, formative and primed pluripotency. Moreover, ESCs with double-knockouts of Tet1 and Tet2 or triple-knockouts of Tet1, Tet2 and Tet3 are phenotypically indistinguishable. These TET-deficient ESCs exhibit differentiate defects; they fail to activate somatic gene expression and retain expression of pluripotency transcription factors. Therefore, TET1 and TET2, but not TET3 act redundantly to facilitate somatic differentiation. Importantly however, TET-deficient ESCs can differentiate into primordial germ cell-like cells (PGCLCs), and do so at high efficiency in the presence or absence of PGC-promoting cytokines. Moreover, acquisition of a PGCLC transcriptional programme occurs more rapidly in TET-deficient cells. These results establish that TET proteins act at the juncture between somatic and germline fates: without TET proteins, epiblast cell differentiation defaults to the germline.

Authors: Raphaël Pantier, Elisa Barbieri, Sara Gonzalez Brito, Ella Thomson, Tülin Tatar, Douglas Colby, Man Zhang, Ian Chambers

Last Update: 2024-12-03 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.12.02.626356

Source PDF: https://www.biorxiv.org/content/10.1101/2024.12.02.626356.full.pdf

Licence: https://creativecommons.org/licenses/by/4.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

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