Hematopoietic stem cell niche

Many human blood cells, such as red blood cells (RBCs), immune cells, and even platelets all originate from the same progenitor cell, the hematopoietic stem cell (HSC). As these cells are short-lived, there needs to be a steady turnover of new blood cells and the maintenance of an HSC pool. This is broadly termed hematopoiesis. This event requires a special environment, termed the hematopoietic stem cell niche, which provides the protection and signals necessary to carry out the differentiation of cells from HSC progenitors. This niche relocates from the yolk sac to eventually rest in the bone marrow of mammals. Many pathological states can arise from disturbances in this niche environment, highlighting its importance in maintaining hematopoiesis. Many human blood cells, such as red blood cells (RBCs), immune cells, and even platelets all originate from the same progenitor cell, the hematopoietic stem cell (HSC). As these cells are short-lived, there needs to be a steady turnover of new blood cells and the maintenance of an HSC pool. This is broadly termed hematopoiesis. This event requires a special environment, termed the hematopoietic stem cell niche, which provides the protection and signals necessary to carry out the differentiation of cells from HSC progenitors. This niche relocates from the yolk sac to eventually rest in the bone marrow of mammals. Many pathological states can arise from disturbances in this niche environment, highlighting its importance in maintaining hematopoiesis. Hematopoiesis involves a series of differentiation steps from one progenitor cell to a more committed cell type, forming the recognizable tree seen in the adjacent diagram. Pluripotent long-term (LT)-HSCs self-renew to maintain the HSC pool, as well as differentiate into short-term (ST)-HSCs. Through various knock-out models, several transcription factors have been found to be essential in this differentiation, such as RUNX1 and SCL. ST-HSCs can then differentiate into either the common myeloid progenitor (CMP) or the common lymphoid progenitor (CLP). The CLP then goes on to differentiate into more committed lymphoid precursor cells. The CMP can then further differentiate into the megakaryocyte–erythroid progenitor cell (MEP), which goes on to make RBCs and platelets, or the granulocyte/macrophage progenitor (GMP), which gives rise to the granulocytes of the innate immune response. MEP differentiation was found to be contingent upon the transcription factor GATA1, whereas GMP differentiation needs SPI1. When expression of either was inhibited by morpholino in zebrafish, the other lineage programming pathway resulted.