Hematopoietic Stem Cells: Nature and Niche Nurture

The document provides a comprehensive review of hematopoietic stem cells (HSCs), challenging the traditional view of HSCs as a homogeneous population and instead presenting evidence of their heterogeneity and lineage affiliations. It discusses the role of cytokines not only in survival and proliferation but also in instructing cell lineage choice, highlighting the complexity of replicating hematopoiesis ex vivo. The review also explores the flexibility of HSCs and hematopoietic progenitor cells (HPCs) in lineage commitment, influenced by both intrinsic factors like gene expression fluctuations and extrinsic factors such as cytokine signaling and chromatin structure. Furthermore, it connects the nature of HSCs to hematopoietic malignancies, particularly leukemia, and the role of oncogenes and cytokines in the survival of leukemia progenitor cells. The document underscores the importance of understanding HSC development and interactions with their niche for advancements in regenerative medicine and the engineering of ex vivo niches for hematopoiesis.