Halyna Shcherbata

Gene Expression and Signaling

Biological roles of miRNAs in stem cell differentiation and maintenance under normal, stress, and disease conditions in Drosophila

Our lab is focused on dissecting the biological roles of miRNAs in cell differentiation and maintenance under normal, stress, and pathological conditions in the fruit fly Drosophila. We show that the miRNA-based regulatory network is accomplished via feedback-feedforward signaling, which reduces transcriptional noise and fine-tunes gene expression to regulate the entire gene expression profile. miRNAs influence cell proliferation and differentiation programs; thus, if miRNA levels are misregulated under stress or pathological states, tissue regeneration and homeostasis are severely disrupted.

A main focus of our research is the analysis of the Dystrophin Glycoprotein Complex, perturbations of which lead to muscular dystrophies and brain abnormalities in humans. We found that stress induces muscle degeneration even in wild type animals and accelerates age-dependent muscular dystrophy and that miRNAs are involved in this process. Future in depth analysis of the interactions of the Dystrophin Glycoprotein Complex components and their regulatory miRNAs will help to understand how the Dystrophin Glycoprotein Complex is regulated under normal and stress conditions.

The second line of the research that is actively conducted in my lab is focused on studying the role of the microRNA pathway in stem cells, where the Drosophila germline and neuronal stem cells are used as model systems. Our findings show that hormonal signaling and miRNAs direct neuronal and germline stem cell differentiation. Not only do steroid hormones control miRNA expression, miRNAs also act in feedback loops to regulate the strength of hormonal signaling.

These regulatory loops fine-tune the signals managing stem cell division, maintenance, and differentiation in response to ever-changing external conditions.

In summary, we found that miRNAs act as

  • Spatio-temporal cell fate determinants
  • Differentiation guardians
  • Stress response elements

Taken together, based on our findings, we believe that miRNAs play a role in generating biological robustness as canalization factors to buffer gene expression against perturbation or variability.

 
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