Hematopoietic stem cells (HSCs) are multipotent stem cells that give rise to all the blood cell types including myeloid (monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes/platelets, dendritic cells), and lymphoid lineages (T-cells, B-cells, NK-cells). The definition of hematopoietic stem cells has undergone considerable revision in the last two decades. The hematopoietic tissue contains cells with long-term and short-term regeneration capacities and committed multipotent, oligopotent, and unipotent progenitors. HSCs constitute 1:10.000 of cells in myeloid tissue.
Intriguingly, HSC do not form a uniform population. Rather, it was shown in a series of landmark experiments between 2002 and 2004 that HSC fall into 16 classes with distinct repopulation kinetics, and 3 categories of lineage bias distinguished by their ratio of lymphoid to myeloid progeny (L/M) in blood. Myeloid-biased (My-bi) HSC have low L/M ratio (>0, <3), while lymphoid-biased (Ly-bi) HSC show a large ratio (>10). The third category consists of the balanced (Bala) HSC for which 3 ≤ L/M ≤ 10. Stem cells in all three classes are true HSC, their behavior is epigenetically fixed and, together, they make up the complete hematopoietic stem cell compartment. The finding of diversity among HSC contradicts older models, which postulated a single type of HSC that can be continuously molded into different subtypes of HSCs.