A 3D Atlas of Hematopoietic Stem and Progenitor Cell Expansion by Multi-Dimensional RNA-Seq Analysis

Abstract

In vertebrates, hematopoiesis occurring in different niches is orchestrated by intrinsic and extrinsic regulators, which are indispensable for the maintenance of homeostasis in a whole organism. Previous studies have revealed a large number of linear and planar regulatory mechanisms. However, a multi-dimensional transcriptomic atlas of any given hematopoietic organ has not been yet established. Here, we use multiple RNA-seq approaches, including cell type-specific temporal bulk RNA-seq, in vivo GEO-seq, and single-cell RNA-seq (scRNA-seq), to characterize the detailed spatiotemporal transcriptome during hematopoietic stem and progenitor cell (HSPC) expansion in the caudal hematopoietic tissue (CHT) of zebrafish. Combinatorial expression profiling reveals that in the CHT niche, HSPCs and their neighboring supporting cells are co-regulated by shared signaling pathways and intrinsic factors, such as integrin signaling and Smchd1. Moreover, scRNA-seq analysis unveils the strong association between cell cycle status and HSPC differentiation. Taken together, we report a global transcriptome landscape that provides valuable insights and a rich resource for understanding HSPC development, particularly on HSPC expansion in an intact hematopoietic organ. The key signaling pathways and factors identified here would contribute to HSPC expansion in vitro.