Blood Development: Hematopoietic Stem Cell Dependence and Independence

Evidence of the diversity and multi-layered organization of the hematopoietic system is leading to new insights that may inform ex vivo production of blood cells. Interestingly, not all long-lived hematopoietic cells derive from hematopoietic stem cells (HSCs). Here we review the current knowledge on HSC-dependent cell lineages and HSC-independent tissue-resident hematopoietic cells and how they arise during embryonic development. Classical embryological and genetic experiments, cell fate tracing data, single-cell imaging, and transcriptomics studies provide information on the molecular/cell trajectories that form the complete hematopoietic system. We also discuss the current developmentally informed efforts toward generating engraftable and multilineage blood cells.The authors thank Lluis Espinosa for critical reading of the review and lab members for helpful discussions. We acknowledge the support of the ERC Advanced Grant (341096 DENOVOHSC) to E.D. and SAF2016-75613-R from MINECO and PERIS- SLT002/16/00299 and 2017SGR135 from Generalitat de Catalunya to A.B