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Tiny Molecules, Big Impact: The Role of MicroRNAs

Discover how microRNAs influence stem cells and health.

Perinthottathil Sreejith, Joshuah Yon, Kalina Lapenta, Benoit Biteau

― 6 min read


MicroRNAs: Key to Stem MicroRNAs: Key to Stem Cell Control health and cellular behavior. Exploring microRNAs' critical roles in
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MicroRNAs (miRs) are tiny molecules that play a big role in how our cells work. They help control many important processes in our bodies, like how cells grow, divide, and change into different types. Scientists have found that even though these little guys come from different types of living things, many of their sequences are the same across species. This shows that they help with really important functions that are similar in all life forms.

For example, in flies (which may not seem significant at first), microRNAs are essential for stem cell development. These special cells can become various types of cells in the body, and they play a critical role in producing new cells that keep tissues healthy. In female and male flies, several microRNAs are required for the development and functioning of stem cells that produce eggs and sperm.

The Role of MicroRNAs in Stem Cells

MicroRNAs help control how stem cells behave. In the learning process about fly biology, scientists found that one widely studied microRNA, called let-7, targets specific messenger molecules in the fly’s testis. If levels of let-7 drop, flies can lose their sperm-producing stem cells as they age. Another microRNA, called bantam, plays a similar role in various types of stem cells, including those in the ovary, the brain, and even the intestines.

In flies, the gut is kept healthy by special cells called Intestinal Stem Cells (ISCs). These cells are the only ones that can divide and create new cells for the gut lining. As these ISCs make new cells, they also generate enteroblasts (EBs), which turn into different types of gut cells. This process is crucial to keeping the gut working well, especially when it’s damaged. When the gut faces injury, like from certain chemicals or bacteria, ISCs spring into action, increasing cell production to repair the damage.

Recently, scientists have started to investigate how various microRNAs affect these intestinal stem cells. Some studies have shown that certain microRNAs can influence how these stem cells behave, including how they differentiate into other cell types and how they respond to stress.

Current Research on MicroRNAs in Drosophila

Research on microRNAs in flies has revealed a lot about how they work in stem cells. For instance, one study pointed out several noteworthy findings:

  1. miR-8: This microRNA is known to influence how stem cells differentiate in the gut.
  2. miR-305: This one has an important role in how ISCs respond to insulin signals, which are crucial for their growth and functioning.
  3. bantam: Another important microRNA for ISCs, it regulates how quickly ISCs can renew themselves.
  4. miR-277: This microRNA impacts energy use in ISCs, making it crucial for their survival.

These findings are part of a larger picture of how microRNAs work with different signals to support the gut's health. The studies suggest that if we want to understand how stem cells function in the gut and beyond, we need to know more about the specific microRNAs that are active in these cells.

Isolating these cells and analyzing their microRNA content is important. Scientists do this through methods like small RNA sequencing, which allows them to examine which microRNAs are expressed in the stem and progenitor cells of the gut.

What Happens if MicroRNAs Don’t Work Right?

MicroRNAs are critical for the proper functioning of stem cells. When scientists disrupt the production of certain microRNAs in the gut, they see significant changes. For example, knocking down Dicer-1, a key player in making microRNAs, reduces the number of intestinal stem cells. Without enough microRNAs, the gut doesn’t repair itself as effectively, which can lead to various health issues.

Analyzing MicroRNAs in the Gut

A group of scientists sought to identify which microRNAs are found in the intestinal stem cells and their early progenitors. To do this, they isolated thousands of GFP-positive cells, which are marked for identification, from the gut. They then sequenced the small RNA populations from these cells and identified numerous microRNAs that were present.

They discovered a total of 63 microRNAs that could be reliably detected, including well-known ones like bantam, miR-275, and miR-305. The researchers also looked for differences in the levels of these microRNAs when Dicer-1 was knocked down. Some microRNAs decreased in number, while others increased, giving hints about which ones might be more active in stem cells versus enteroblasts.

The Effects of Specific MicroRNAs on Intestinal Stem Cells

The research focused on two microRNAs that have shown particular promise in regulating intestinal stem cells: miR-31a and miR-34.

The Role of miR-31a

The researchers found that miR-31a is a negative regulator of ISC proliferation. In simple terms, this means that when miR-31a is present in higher amounts, it stops stem cells from dividing too much. Using specific experiments, scientists manipulated the levels of miR-31a and saw that when they reduced its function, the stem cells grew much faster. Conversely, when they increased miR-31a levels, the growth of stem cells slowed down significantly.

In a fun twist, during stress testing with DSS (a harmful chemical), the overexpression of miR-31a completely halted the response that normally promotes cell growth. Meanwhile, reducing miR-31a didn’t significantly change how stem cells responded under stress, hinting that its role might be more about controlling their return to a resting state after they’ve done their job.

The Role of miR-34

Similarly, miR-34 has a critical function as well. This microRNA is known to affect growth and division, and researchers found that flies lacking miR-34 had very few enteroblasts in their guts. When researchers exposed these flies to stress, they observed that the usual increase in cell production did not happen.

However, when miR-34 was overexpressed, it caused a strong drop in cell proliferation, especially when applied to stem cells directly. Interestingly, this suggests that miR-34 also plays an essential role in how ISCs respond to stress and maintain their proper function.

Conclusion: The Fascinating World of MicroRNAs

MicroRNAs are tiny but mighty players in the world of molecular biology. They regulate how cells behave, grow, and respond to stress. The ongoing research into microRNAs in the intestinal stem cells of flies shines a light on their importance not just in flies, but potentially in human health as well.

By understanding how these microRNAs work, scientists hope to gain insight into various biological processes, including aging, development, and even diseases like cancer. After all, if tiny molecules can control the fate of cells, imagine what other secrets they may hold!

So, the next time you munch on a snack, remember that even the smallest things can have the biggest impacts. Just like that tiny sprinkle of salt can change a whole dish, microRNAs are changing the course of science and our understanding of life itself!

Original Source

Title: MicroRNA profiling identifies novel regulators of stem cell function in the adult Drosophila intestine.

Abstract: Precise control of stem cell activity is critical to maintain homeostasis and regenerative capacity of adult tissues and limit proliferative syndromes. Hence, stem cell-specific complex regulatory networks exist to exquisitely maintain gene expression and adapt it to tissue demand, controlling self-renewal, fate commitment and differentiation of developing and adults cell lineages. One of the essential and conserved regulatory components that fine-tune gene expression are microRNAs, which post-transcriptionally regulate stability and translation of messengers. microRNAs have been identified as critical stem cell regulators across stem cell populations and organisms. Here, we report the profiling of microRNAs expressed in stem cells and their immediate daughter cells in the Drosophila adult intestine. Our analysis identifies over 60 miRs that can be reliably detected in these sorted progenitor cells; a few of these have been reported to control fly intestinal stem cells, but most have yet to be investigated in the adult intestinal lineage. To validate the relevance of our unbiased analysis, we chose to characterize the phenotypes associated with genetic manipulations of two of these microRNAs, miR-31a and miR-34, which are conserved in other organisms, but whose function has not been investigated in the Drosophila midgut. We found that miR-31a acts as anti-proliferation factor and is important for the re-entry of ISC into quiescence after tissue damage. Additionally, we demonstrate that miR-34 is essential for ISC proliferation, but its over-expression also prevents proliferation, highlighting the complexity of miR-mediated control of stem cell function. Altogether, our work establishes a new critical resource to investigate the detailed mechanisms that control stem cell proliferation and intestinal differentiation under homeostatic conditions, in response to tissue damage, or during epithelial transformation and aging.

Authors: Perinthottathil Sreejith, Joshuah Yon, Kalina Lapenta, Benoit Biteau

Last Update: 2024-12-30 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.12.30.630748

Source PDF: https://www.biorxiv.org/content/10.1101/2024.12.30.630748.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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