Age-dependent regulation of hematopoiesis by megakaryocytes

Recent studies have expanded the concept of the bone marrow niche beyond stromal cells to include differentiated hematopoietic progeny as direct regulators of hematopoietic stem cells (HSCs). Among these, megakaryocytes have emerged as key niche regulators of HSC function across homeostasis, stress responses, aging, and disease. This review summarizes recent advances defining how aging alters megakaryocyte-mediated regulation of hematopoiesis.

Megakaryocytes regulate HSC quiescence, lineage output, and stress responsiveness through spatial organization within the bone marrow microenvironment and the production of niche-derived factors. Recent studies revealed that aging is associated with changes in megakaryocyte abundance, maturation state, and transcriptional and secretory programs, resulting in altered niche functions and hematopoiesis. These findings establish megakaryocytes as dynamic niche components whose regulatory roles evolve across the lifespan.

Age-dependent remodeling of the megakaryocytic niche provides a conceptual framework for understanding how hematopoietic regulation is reprogrammed with aging. Targeting megakaryocyte-derived niche signals may offer new opportunities to rejuvenate hematopoiesis and improve outcomes in age-associated hematopoietic disorders.