On the origin of hematopoietic stem cells: Progress and controversy

Hematopoietic Stem Cells (HSCs) are responsible for the production and replenishment of all blood cell types during the entire life of an organism. Generated during embryonic development, HSCs transit through different anatomical niches where they will expand before colonizing in the bone marrow, where they will reside during adult life. Although the existence of HSCs has been known for more than fifty years and despite extensive research performed in different animal models, there is still uncertainty with respect to the precise origins of HSCs. We review the current knowledge on embryonic hematopoiesis and highlight the remaining questions regarding the anatomical and cellular identities of HSC precursors.

► The review summarizes the hematopoietic development in different animal models. ► We discuss the possible anatomical origins of hematopoietic stem cells. ► We document the endothelial origin of hematopoietic stem cells. ► We address the remaining questions about hematopoietic stem cell generation.