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Stochasticity Open Seminar June 13, 2017, 12:00

Open Seminars of the Research Group on


Stochasticity and Control in the Dynamics and Diversity of Immune Repertories: an Example of Multi-Cellular Co-Operation


Tuesday, June 13, 2017, 12:00

at the Israel Institute for Advanced Studies, Room 128




Challenges in extracting splicing bias from single cell RNA sequencing data


Tal Shay (BGU)


Hematopoietic stem cells (HSCs) differentiate into all blood and immune cell types. As a population, HSCs express many genes, and for the vast majority of those genes, many isoforms. Single cell RNA sequencing (scRNA-seq) has revolutionized the understanding of cell population heterogeneity in many biological systems. In particular, for HSCs, scRNA-seq revealed lineage priming, clonality, and differentiation trajectories. However, the isoform usage at the single HSC level and its regulation are still unknown.

We collected publicly available murine HSCs scRNA-seq datasets and identified genes for which HSCs display splicing bias, where the single cell splicing isoforms usage is significantly different from the population level usage. Apparent splicing bias can be affected by amplification bias, random loss of molecules, low coverage and other technical factors. As splicing bias is consistent between datasets produced by scRNA-seq protocols, it seems to reflect a real biological bias of the cells, whose regulation and functional consequence remains to be studied. 



Related Research Questions


  1. What are the regulatory mechanism of RNA splicing?
  2. Is the splicing isoforms mixture in each cell a random sample of the splicing isoforms mixture of the cell population?
  3. Is the splicing isoforms mixture in each cell stochastic or regulated?



Suggested Reading


Computational and analytical challenges in single-cell transcriptomics

O. Stegle, S. A. Teichmann, J. C. Marioni

Nature Reviews Genetics 16, 133–145 (2015)



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