Adult murine hematopoietic stem cells and progenitors: an update on their identities, functions, and assays

The founder of all blood cells are hematopoietic stem cells (HSCs), which are rare stem cells that undergo key cell fate decisions to self-renew to generate more HSCs or to differentiate progressively into a hierarchy of different immature hematopoietic cell types to ultimately produce mature blood cells. These decisions are influenced both intrinsically and extrinsically, the latter by microenvironment cells in the bone marrow (BM). In recent decades, notable progress in our ability to identify, isolate, and study key properties of adult murine HSCs and multipotent progenitor (MPP) cells has challenged our prior understanding of the hierarchy of these primitive hematopoietic cells. These studies have revealed the existence of at least two distinct HSC types in adults: one that generates all hematopoietic cell lineages with almost equal potency and one that is platelet/myeloid-biased and increases with aging. These studies have also revealed distinct MPP cell types that have different functional potential. This review provides an update to these murine HSCs and MPP cells, their key functional properties, and the assays that have been used to assess their potential.