Quantitative molecular cartography of emergency myelopoiesis reveals conserved modules of hematopoietic activation
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Hematopoietic stem and progenitor cells (HSPC) respond to infections, inflammation, and regenerative challenges using a collection of cellular and molecular mechanisms termed emergency myelopoiesis (EM) pathways. However, it remains unclear how various EM inducers regulate HSPCs using shared or distinct molecular mechanisms. Here, we generate a comprehensive and generalizable cell annotation method (HemaScribe) and a refined quantitative model of hematopoietic differentiation (HemaScape) using single cell RNA sequencing (scRNA-seq) of HSPCs, which we apply to a broad range of EM modalities. We uncover multiple strategies to enhance myelopoiesis acting at different levels of the HSPC hierarchy, which are associated with both unique and shared transcriptional response modules. In particular, we identify a myeloid progenitor-based module of EM engagement across diverse inflammatory challenges, which informs outcome in adult and pediatric human acute myeloid leukemia. Collectively, our work illuminates fundamental regulatory mechanisms in hematopoietic regeneration that have direct translational applications in disease contexts.
HIGHLIGHTS
-
New HemaScribe method for hematopoietic progenitor annotation in scRNA-seq datasets
-
Different emergency myelopoiesis (EM) inducers act at distinct hematopoiesis levels
-
Unique and shared transcriptional response modules enacted by different EM inducers
-
A myeloid progenitor EM module informs outcome in acute myeloid leukemia
eTOC BLURB
Swann et al. conduct comparative analysis of single cell RNA sequencing data from multiple emergency myelopoiesis models, finding that different perturbations act at various levels of the hematopoietic hierarchy and recruit distinct sets of molecular mechanisms to enhance myelopoiesis. In particular, they identify a conserved myeloid progenitor-based activation module across multiple disease conditions, which informs outcome in human acute myeloid leukemia.
