FateID infers cell fate bias in multipotent progenitors from single-cell RNA-seq data

• Published in: bioRxiv
• Main Authors: Herman, Josip Stefan, Sagar, Sagar, Grun, Dominic
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 11.11.2017; Cold Spring Harbor Laboratory
• Edition: 1.1
• Subjects: Bias; Bioinformatics; Bone marrow; Cell differentiation; Cell fate; Computer applications; Dendritic cells; Gene expression; Hemopoiesis; Lymphocytes B; Ribonucleic acid; RNA
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/218115

Differentiation of multipotent cells is a complex process governed by interactions of thousands of genes subject to substantial expression fluctuations. Resolving cell state heterogeneity arising during this process requires quantification of gene expression within individual cells. However, computational methods linking this heterogeneity to biases towards distinct cell fates are not well established. Here, we perform deep single-cell transcriptome sequencing of ~2,000 bone-marrow derived mouse hematopoietic progenitors enriched for lymphoid lineages. To resolve subtle transcriptome priming indicative of distinct lineage biases, we developed FateID, an iterative supervised learning algorithm for the probabilistic quantification of cell fate bias. FateID delineates domains of fate bias within progenitor populations and permits the derivation of high-resolution differentiation trajectories, revealing a common progenitor population of B cells and plasmacytoid dendritic cells, which we validated by in vitro differentiation assays. We expect that FateID will enhance our understanding of the process of cell fate choice in complex multi-lineage differentiation systems.