From bud to stem: dynamics of hematopoietic stem cells that drive homing and mobilization

Hematopoietic stem and progenitor cells (HSPCs) ensure lifelong hematopoiesis through their unique ability to self-renew and differentiate into all blood cell lineages. Their localization within bone marrow niches and the ability to traffic between hematopoietic and peripheral tissues during development and adult life are governed by complex signaling networks involving adhesion molecules, chemokines, metabolic cues, and niche-derived factors.

This review explores the molecular and cellular mechanisms that regulate HSPC homing, retention, and mobilization during development, homeostasis, and therapeutic transplantation. In particular, we focus on intrinsic, dynamic properties of HSPCs that guide developmental transitions in trafficking behavior from fetal to adult niches, physiological egress under steady-state conditions, and dictate outcomes of forced mobilization and bone marrow homing during therapeutic collection and transplantation.

These findings highlight HSPC trafficking as a highly regulated and adaptable process integrating intrinsic stem cell states with extrinsic niche cues. Understanding these mechanisms provides a conceptual framework for improving strategies to enhance HSPC mobilization, homing, and engraftment toward optimizing hematopoietic stem cell therapies.