An interactive resource of molecular signalling in the developing human haematopoietic stem cell (HSC) niche

Edie I Crosse, Anahi Binagui-Casas, Sabrina Gordon-Keylock, Stanislav Rybtsov, Sara Tamagno, Didrik Olofsson, Richard A Anderson, Alexander Medvinsky

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The emergence of definitive human haematopoietic stem cells (HSCs) from Carnegie Stage (CS) 14 to CS17 in the aorta-gonad-mesonephros (AGM) region is a tightly regulated process. Previously, we conducted spatial transcriptomic analysis of the human AGM region at the end of this period (CS16/CS17) and identified secreted factors involved in HSC development. Here, we extend our analysis to investigate the progression of dorso-ventral polarised signalling around the dorsal aorta over the entire period of HSC emergence. Our results reveal a dramatic increase in ventral signalling complexity from the CS13-CS14 transition, coinciding with the first appearance of definitive HSCs. We further observe stage-specific changes in signalling up to CS17, which may underpin the step-wise maturation of HSCs described in the mouse model. The data-rich resource is also presented in an online interface enabling in silico analysis of molecular interactions between spatially defined domains of the AGM region. This resource will be of particular interest for researchers studying mechanisms underlying human HSC development as well as those developing in vitro methods for the generation of clinically relevant HSCs from pluripotent stem cells.

Original languageEnglish
Article numberdev201972
Number of pages46
Issue number23
Early online date16 Oct 2023
Publication statusPublished - 1 Dec 2023

Keywords / Materials (for Non-textual outputs)

  • Haematopoiesis
  • Human Development
  • Spatial Transcriptomics
  • Single cell RNA-Seq
  • AGM region


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