Introduction to a review series on hematopoietic stem cells

Hematopoietic stem cells (HSCs) are responsible for the lifelong production of all blood lineages; therefore, their specification and maintenance are tightly regulated. Many studies have leveraged murine models of hematopoiesis to provide basic insights into HSC biology and have defined HSCs based on murine cell surface markers, which are not fully recapitulated in humans. In this review series, experts in the field highlighted several aspects of HSC biology, ranging from ontogeny to aging and leukemia transformation, with an emphasis on the development and characterization of human HSCs. The following articles are included:

• Fernando Anjos-Afonso and Dominique Bonnet, “Human CD34⁺ hematopoietic stem cell hierarchy: how far are we with its delineation at the most primitive level?”

• Vincenzo Calvanese and Hanna K. A. Mikkola, “The genesis of human hematopoietic stem cells”

• Patricia A. Colom Díaz, Jayna J. Mistry, and Jennifer J. Trowbridge, “Hematopoietic stem cell aging and leukemia transformation”

• Maria Jassinskaja, Monika Gonka, and David G. Kent, “Resolving the hematopoietic stem cell state by linking functional and molecular assays”

Several themes emerged from this review series. First, there have been substantial advances in our understanding of human pre- and postnatal hematopoiesis. Second, there is a pressing need to accelerate the progress in defining a pure population of human HSCs. Third, new approaches are necessary to allow for the simultaneous evaluation of HSC functional activity and its molecular state through multiomics assays. Finally, methods to target both intrinsic and extrinsic factors that contribute to the functional decline of HSCs during aging require refinement.

We hope that this review series will stimulate research to expand our understanding of the biology of this critical cell population, develop novel strategies to reverse the effects of aging, prevent malignant transformation, and enhance the in vitro production of HSCs from pluripotent stem cells.