Hematopoietic stem cells (HSCs) are multipotent stem cells primarily residing in the bone marrow, responsible for the lifelong production and regeneration of all blood cell lineages through the process of hematopoiesis. These rare cells possess two defining properties: self-renewal, allowing them to maintain their population, and multilineage differentiation potential, enabling them to generate both myeloid and lymphoid blood cells. HSCs are also found in peripheral blood and umbilical cord blood, with distinct functional properties depending on their source. Understanding the molecular mechanisms governing HSC self-renewal, differentiation, and migration is critical for advancing regenerative medicine and improving therapeutic strategies such as hematopoietic stem cell transplantation (HSCT).

Subtypes and Hierarchical Organization

HSCs can be classified based on their repopulation capacity into long-term HSCs (LT-HSCs), short-term HSCs (ST-HSCs), and multipotent progenitors (MPPs). LT-HSCs are the most primitive subset with durable self-renewal ability, capable of sustaining hematopoiesis over the lifetime of an organism. ST-HSCs and MPPs have limited self-renewal but retain multilineage differentiation potential and contribute to rapid blood cell replenishment during stress or injury. The hierarchical differentiation model posits that HSCs give rise to lineage-committed progenitors, which further differentiate into mature blood cells. The two major lineages derived from HSCs are myeloid cells (erythrocytes, megakaryocytes/platelets, monocytes, granulocytes) and lymphoid cells (T cells, B cells, natural killer cells).

Functional Roles and Clinical Relevance

HSCs maintain hematopoietic homeostasis by balancing quiescence and activation in response to physiological demands. They migrate between bone marrow, peripheral blood, and other hematopoietic sites, such as the thymus and spleen, especially under stress conditions. Clinically, HSCs are the cornerstone of bone marrow and stem cell transplantation therapies used to treat hematologic malignancies, immune deficiencies, and other blood disorders. Advances in HSC culture, expansion, and mobilization techniques have improved transplantation outcomes. Moreover, HSCs exhibit plasticity, with reports of transdifferentiation into non-hematopoietic lineages such as endothelial and neural cells, broadening their therapeutic potential beyond hematopoiesis.

Key Search Terms for Hematopoietic Stem Cells

• Hematopoietic stem cells

• Long-term and short-term HSCs

• Multipotent progenitors hematopoiesis

• HSC self-renewal and differentiation

• Myeloid and lymphoid lineage commitment

• Hematopoietic stem cell transplantation

• HSC mobilization and migration

• Bone marrow hematopoietic niche

• HSC plasticity and transdifferentiation

• Regenerative medicine hematopoietic cells