mRNA Dynamics Guide Cell Identity Formation

New research from Hebrew University sheds light on the regulation of mRNA during the development of the embryo. The research separates newly-transcribed from pre-existing mRNA in zebrafish embryos using a combination of single-cell RNA-Seq and metabolic labeling.

This method measures the rates of mRNA transcription and degradation within distinct cell types, revealing different gene-specific regulatory rates as well as degradation variations between cell types. Deciphering how genes are turned on and off in particular cells at specific times, as well as potential applications in medicine and biology, is made easier with an understanding of mRNA regulation during embryonic development.

In collaboration with researchers from the National Institutes of Health in the USA, a new study led by Ph.D. Student Lior Fishman and team at The Alexander Silberman Institute of Life Science at Hebrew University, guided by researcher Dr. Michal Rabani, illuminate the complex process of mRNA regulation during embryonic development, offering fresh perspectives on how pluripotent cells take on specialized identities through gene expression.

During the process of embryonic development, pluripotent cells take on specific identities through the adoption of specific gene expression profiles. It has proven difficult to determine how much each mRNA transcription and degradation contributed to the formation of these profiles, especially in embryos with different cellular identities.

Researchers tracked how genes are turned on and off over time in zebrafish embryos using metabolic labeling and a technique called single-cell RNA sequencing. They were able to distinguish between the mRNA that came from the embryo itself and the mRNA that came from the mother. They measured the rate at which different types of cells turned on and off their genes during development using mathematical models.

Thousands of genes have very different regulatory rates, according to the study's findings. The researchers connected variations in degradation to particular sequence elements after observing coordinated transcription and destruction rates for numerous transcripts.

Significantly, they discovered degradation variations specific to different cell types, such as the selective retention of maternal transcripts in enveloping layer cells and primordial germ cells - two of the first cell types to be identified.

Our study provides a quantitative approach to studying mRNA regulation during a dynamic spatio-temporal response. This work opens up new avenues for understanding the molecular mechanisms underlying cell fate determination during embryonic development.”

Dr. Michal Rabani, Study Senior Author, The Hebrew University of Jerusalem

The results obtained from this investigation enhance our comprehension of mRNA regulation and its function in molding cellular identities throughout the process of embryonic development.

The research team anticipates that their efforts will open up new avenues for investigations into the intricacies of controlling gene expression in diverse biological settings.

Journal reference:

Fishman, L., et al. (2024) Cell-type-specific mRNA transcription and degradation kinetics in zebrafish embryogenesis from metabolically labeled single-cell RNA-seq. Nature Communications.


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