PT  - JOURNAL ARTICLE
AU  - Klebea Carvalho
AU  - Elisabeth Rebboah
AU  - Camden Jansen
AU  - Katherine Williams
AU  - Andrew Dowey
AU  - Cassandra McGill
AU  - Ali Mortazavi
TI  - Uncovering the Gene Regulatory Networks Underlying Macrophage Polarization Through Comparative Analysis of Bulk and Single-Cell Data
AID  - 10.1101/2021.01.20.427499
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.01.20.427499
4099  - http://biorxiv.org/content/early/2021/01/21/2021.01.20.427499.short
4100  - http://biorxiv.org/content/early/2021/01/21/2021.01.20.427499.full
AB  - Gene regulatory networks (GRNs) provide a powerful framework for studying cellular differentiation. However, it is less clear how GRNs encode cellular responses to everyday microenvironmental cues. Macrophages can be polarized and potentially repolarized based on environmental signaling. In order to identify the GRNs that drive macrophage polarization and the heterogeneous single-cell subpopulations that are present in the process, we used a high-resolution time course of bulk and single-cell RNA-seq and ATAC-seq assays of HL-60-derived macrophages polarized towards M1 or M2 over 24 hours. We identified transient M1 and M2 markers, including the main transcription factors that underlie polarization, and subpopulations of naive, transitional, and terminally polarized macrophages. We built bulk and single-cell polarization GRNs to compare the recovered interactions and found that each technology recovered only a subset of known interactions. Our data provide a resource to study the GRN of cellular maturation in response to microenvironmental stimuli in a variety of contexts in homeostasis and disease.Competing Interest StatementThe authors have declared no competing interest.