[Advances in hematopoietic development]

Hematopoietic stem cells (HSCs) sustain lifelong blood production, and understanding their developmental origin is a central focus in both basic and translational research. During embryogenesis, HSCs originate from arterial endothelial cells in the aorta-gonad-mesonephros (AGM) region. These endothelial cells give rise to hemogenic endothelial cells that subsequently undergo endothelial-to-hematopoietic transition (EHT) to generate HSCs. This process is regulated by transcription factors centered around RUNX1 and stage-specific signaling cues. Recent advances in in vitro culture systems have enabled the reconstruction of these developmental processes, facilitating the identification of HSC precursors and the signaling pathways required for their maturation. These insights have driven significant progress toward generating HSCs from human pluripotent stem cells, particularly induced pluripotent stem cells (iPSCs). Notably, HSC-like cells with multilineage potential and long-term engraftment capacity have been induced using stepwise, developmentally guided conditions without genetic manipulation. However, challenges remain, including low efficiency, cellular heterogeneity, and limitations of in vivo evaluation systems. This review summarizes the current understanding of HSC development, advances in culture-based reconstruction, and progress and challenges in deriving HSCs from human iPSCs.