Do lincRNAs Contribute to Mouse Embryonic Stem Cell Cycle Adaptations?

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Event details

Date 22.08.2017
Hour 11:3012:30
Speaker Prof. Ana Claudia Marques, University of Lausanne (CH)
Location
Category Conferences - Seminars
BIOENGINEERING SEMINAR

Abstract:
Intergenic long noncoding RNAs (lincRNAs) are the largest class of transcripts in the human genome and their transcription is pervasive in higher eukaryotes. Functional and evolutionary analyses together with extensive characterization of a handful of lincRNAs support the general consensus that these transcripts contribute to the regulation of gene expression programs and some can impact normal and disease phenotypes.

Recently a number of lincRNAs have been shown to contribute to cell cycle progression. Given that most lincRNA expression is spatially and temporally restricted, we hypothesized that they would contribute to cell-type specific modulation of this process. To test this hypothesis, we focused on the contributions of lincRNAs to embryonic stem cell cycle because compared to differentiated cells the embryonic stem cell cycle is characterized by a truncated G1 phase and an elongated S phase. We used single cell RNA-sequencing data for mouse embryonic stem cells staged at G1, S, or G2/M cell cycle phases to identify genes differentially expressed between these stages. We found that lincRNAs are enriched within differentially expressed genes suggesting their expression is more tightly controlled than that of mRNAs during this key cellular process. Cell cycle associated lincRNAs are co-expressed with protein-coding genes with established roles in cell cycle progression and experimental evidence supports the role some of these transcripts in the modulation of the levels of key cell cycle regulators and influence cell cycle progression. Importantly 70% of cell cycle-associated lincRNAs are differentially expressed between G1 and S suggesting they can contribute to the maintenance of the short G1 phase and a high proportion of cells in S phase that characterize embryonic stem cell cycle. Consistent with this hypothesis G1/S differential expressed lincRNAs are more cell type specific than other cell cycle associated lincRNAs and frequently genetically interact with genes involved in maintenance of pluripotency. Experimental and computational validation of this hypothesis is currently ongoing.

In summary our data suggests that lincRNAs contribute to the mouse embryonic stem cell cycle adaptations.

Bio:
After obtaining her diploma in Chemical Engineering from the Technical University of Lisbon, Ana Marques decided to pursue her interest in the molecular basis of human traits. In 2003, she started her PhD under the supervision of Henrik Kaessmann at the University of Lausanne. During her graduate studies she investigated the contribution of gene duplication to the origin and evolution of human phenotypes. In 2008 she joined Chris Ponting’s group as a post-doctoral fellow to work on the origin and evolution of intergenic lncRNAs. Her postdoctoral training was funded by SNF, FCT and Marie Curie fellowships. In 2012, she was awarded a Research Fellowship (The Royal Society) and started developing an independent research program on the biological and molecular functions of intergenic lncRNAs. Ana Marques has been a Swiss National Science Foundation Professor since October 2014, when she set up lab at UNIL’s Department of Physiology. She is currently a member of the UNIL's Department of Computational Biology.

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