Abstract
Like all cells, hematopoietic stem cells (HSCs) and their offspring, the hematopoietic progenitor cells (HPCs), are highly sociable. Their capacity to interact with bone marrow niche cells and respond to environmental cytokines orchestrates the generation of the different types of blood and immune cells. The starting point for engineering hematopoiesis ex vivo is the nature of HSCs, and a longstanding premise is that they are a homogeneous population of cells. However, recent findings have shown that adult bone marrow HSCs are really a mixture of cells, with many having lineage affiliations. A second key consideration is: Do HSCs “choose” a lineage in a random and cell-intrinsic manner, or are they instructed by cytokines? Since their discovery, the hematopoietic cytokines have been viewed as survival and proliferation factors for lineage committed HPCs. Some are now known to also instruct cell lineage choice. These fundamental changes to our understanding of hematopoiesis are important for placing niche support in the right context and for fabricating an ex vivo environment to support HSC development.
Highlights
Stem Cells: Nature and Nichehematopoietic stem cells (HSCs) produce a wide range of cell types, each with unique functions, that include platelets, erythrocytes, basophils/mast cells, eosinophils, neutrophils, dendritic cells, B lymphocytes, innate lymphoid cells, and T lymphocytes
Unlike the diverse progeny of normal multipotent stem cells, the bulk cells of the hundreds of distinct cancer types resemble just one mature or partially mature cell type, even when the origin is a multipotent stem cell. This is clearly seen for chronic myeloid leukemia (CML) and acute erythroid leukemia, which arise in an HSC with the progeny belonging to just the neutrophil and erythroid lineages, respectively
Stochastic modelling of lineage affiliation is highly suited to describing complex syschoice [79]
Summary
HSCs produce a wide range of cell types, each with unique functions, that include platelets, erythrocytes, basophils/mast cells, eosinophils, neutrophils, dendritic cells, B lymphocytes, innate lymphoid cells, and T lymphocytes. A comprehensive view of mouse hematopoiesis, including the nature of HSCs. In a strict sense, HSCs are able to reconstitute the entire blood and immune progenitor cell populations, iscombined still well in advance (SCID). AHowever, sub-population of HSCs that requiresof thrombopoietin for maintenance, andidentified that sub-populations murine HSCs have been expresses the megakaryocyte-affiliated von Willebrand factor, gave rise to a long-term press or receptors for somereconstitution of the cytokines that are lineage-affiliated. A sub-population of HSCs that requires thrombopoietin for mainte presses the megakaryocyte-affiliated von Willebrand factor, gave rise t let- or platelet/myeloid-biased reconstitution when transplanted as s surface marker CD41 (alph11b integrin, platelet GP11b) further supported the existence of megakaryocyte-biased HSCs [8], and other workers identified such cells with impaired self-renewal [9]. Murine myeloid- and lymphoid-biased HSCs selectively express the cell surface markers CD41 and CD86, respectively. The frequency of multi-lineage chimerism was rather low for both first (28%) and second transfers (14%), in keeping with the heterogeneous nature of HSCs [17]
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