Abstract
Not all hematopoietic stem cells (HSCs) are alike. They differ in their physical characteristics such as cell cycle status and cell surface marker phenotype, they respond to different extrinsic signals, and they have different lineage outputs following transplantation. The growing body of evidence that supports heterogeneity within HSCs, which constitute the most robust cell fraction at the foundation of the adult hematopoietic system, is currently of great interest and raises questions as to why HSC subtypes exist, how they are generated and whether HSC heterogeneity affects leukemogenesis or treatment options. This Review provides a developmental overview of HSC subtypes during embryonic, fetal and adult stages of hematopoiesis and discusses the possible origins and consequences of HSC heterogeneity.
Highlights
Hematopoietic stem cells (HSCs) give rise to all cells in the blood lineage through the process of hematopoiesis
The growing body of evidence that supports heterogeneity within hematopoietic stem cells (HSCs), which constitute the most robust cell fraction at the foundation of the adult hematopoietic system, is currently of great interest and raises questions as to why HSC subtypes exist, how they are generated and whether HSC heterogeneity affects leukemogenesis or treatment options. This Review provides a developmental overview of HSC subtypes during embryonic, fetal and adult stages of hematopoiesis and discusses the possible origins and consequences of HSC heterogeneity
Are HSC subtypes programmed intrinsically during development? Or, do all HSCs begin life identically, with heterogeneity determined by extrinsic factors encountered during the migration and colonisation of HSCs in different developmental tissues and their respective niches? These important issues, as well as the physiological relevance of HSC heterogeneity, are beginning to be addressed
Summary
Hematopoietic stem cells (HSCs) give rise to all cells in the blood lineage through the process of hematopoiesis. Multilineage hematopoietic outputs characterise HSC subtypes in the bone marrow The primary function of an HSC when transplanted into an irradiated/myelodefective adult mouse recipient is the production of mature hematopoietic cells that include cells of the myeloid (granulocyte, macrophage), erythroid, platelet/megakaryocyte and lymphoid (B and T cell) lineages.
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