SNIC SUPR
Approaching Hematopoietic Stem Cell Differentiation Using scRNA-seq
Dnr:

SNIC 2018/3-525

Type:

SNIC Medium Compute

Principal Investigator:

David Bryder

Affiliation:

Göteborgs universitet

Start Date:

2018-10-26

End Date:

2019-11-01

Primary Classification:

30401: Medical Biotechnology (focus on Cell Biology (incl. Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Allocation

Abstract

n a cellular system where diverse mature effector cells are generated from a common precursor, scRNA-seq might have a particular value for de-convolututing relationships in between cells and the developmental progression of cells belonging to the same lineage/s. When cells are sampled at any given point in time, each cell will represent different stages of maturation and/or with different effector functions. With such data at hand, significant efforts have been invested in developing analysis procedures that can order the investigated cells based on developmental progression, a procedure commonly referred to as pseudotiming (or trajectory analysis) – this because the underlying data is based on a snapshot measurement of heterogeneous cells, rather than actual transitions across an investigated time window. While there are several described procedures to establish pseudotime of scRNA-seq data, there is currently no perfect universal solution/analysis framework (https://ww w.biorxiv.org/content/early/2018/03/05/276907). Continuous efforts to develop such procedures are therefore warranted. The overall aims of the current project is: 1) To determine how inference from real timing affects determination of gene networks around hematopoietic lineage-commitment branching points. 2) To determine the impact of aging on hematopoiesis emanating from HSCs, including whether and how gene networks are perturbed around individual lineage branching points. The project will not include any sensitive human data.