Abstract
Hematopoietic stem cells (HSCs) are the best-characterized stem cells in adult tissues. Nevertheless, as of today, many open questions remain. First, what is the phenotype of the most primitive “pre-HSC” able to undergo asymmetric divisions during ex vivo expansion that gives rise to HSC for all hemato-lymphopoietic lineages. Next, most routine in vitro assays designed to study HSC specification into hematopoietic progenitor cells (HPCs) for major hematopoietic lineages are based on a limited number of peptide-based growth factors and cytokines, neglecting the involvement of several other regulators that are endowed with hematopoietic activity. Examples include many hormones, such as pituitary gonadotropins, gonadal sex hormones, IGF-1, and thyroid hormones, as well as bioactive phosphosphingolipids and extracellular nucleotides (EXNs). Moreover, in addition to regulation by stromal-derived factor 1 (SDF-1), trafficking of these cells during mobilization or homing after transplantation is also regulated by bioactive phosphosphingolipids, EXNs, and three ancient proteolytic cascades, the complement cascade (ComC), the coagulation cascade (CoA), and the fibrinolytic cascade (FibC). Finally, it has emerged that bone marrow responds by “sterile inflammation” to signals sent from damaged organs and tissues, systemic stress, strenuous exercise, gut microbiota, and the administration of certain drugs. This review will address the involvement of these unconventional regulators and present a broader picture of hematopoiesis.
Highlights
Hematopoietic stem/progenitor cells (HSPCs) are the beststudied stem cells and have been widely employed in the clinic for 50 years
In addition to bone marrow (BM) as a source of HSPCs [1], cells for transplantations are derived from mobilized peripheral blood [2] and umbilical cord
A major role in the migration of HSPCs has been assigned to the α-chemokine stromal-derived factor 1 (SDF-1) [10, 11]; evidence has accumulated that bioactive phosphosphingolipids [12,13,14] as well as nucleotides secreted into the extracellular space and nucleosides [15,16,17] may affect hematopoietic development and postnatal migration of HSPCs
Summary
Hematopoietic stem/progenitor cells (HSPCs) are the beststudied stem cells and have been widely employed in the clinic for 50 years. In addition to bone marrow (BM) as a source of HSPCs [1], cells for transplantations are derived from mobilized peripheral blood (mPB) [2] and umbilical cord
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