This chapter provides an overview on hematopoietic stem cells (HSCs), which primarily reside in bone marrow, maintain blood formation, and replenish themselves throughout the adult's lifespan. Adult HSCs are relatively dormant under homeostasis but can extensively proliferate when they encounter regenerative stresses. Adult HSCs comprise only ∼0.02% of whole bone marrow cells but possess abilities to self-renew and differentiate (hematopoiesis) to replenish the whole hematopoietic system. A single HSC is sufficient to establish long-term multilineage engraftment, which would only be possible through a self-renewal process. During adult hematopoiesis, BM-HSCs generate both lymphoid and myeloid cells. Lymphoid cells are comprised of primarily T-cells, B cells, and natural killer (NK) cells. Myeloid cells include granulocytes, macrophages, megakaryocytes, and erythrocytes. Hematopoiesis is a gradual differentiation process that involves multiple decision points beginning with HSCs and ending with terminally differentiated lineages. In adults, HSCs reside in the bone marrow cavity, closely associated with surrounding stromal cells. The most primitive HSCs localize to the interior surface of bone (periosteum/endosteum border) on the basis of colony-forming assays and Brd-U label retention, bringing them within close contact with osteoblasts. Molecules including N-cadherin, Notch-1, Tie2, and CXCR-4 are implicated in the HSC-to-niche interface. The identification and purification of long-term (LT)-HSCs relies on combinations of cell surface markers, with the presence or absence of specific antigens allowing discrimination of these cells from other bone marrow cell types including the immediately downstream short-term (ST)-HSCs and progenitor cell compartments.
|Title of host publication||Principles of Regenerative Medicine|
|Number of pages||12|
|State||Published - Dec 1 2011|