Expansion of functional human long-term HSCs through restraining excessive cell cycle activation

The authors investigate how to expand functional human long-term hematopoietic stem cells (HSCs) ex vivo while preserving their self-renewal and multilineage potential, which are often compromised in current culture systems. By employing single-cell multiome sequencing, they identify molecular mechanisms behind the functional decline and myeloid bias of cultured HSCs, and develop a niche-mimetic culture system that effectively maintains HSC characteristics and enhances their expansion. This study provides insights into the preservation of stemness in HSCs during culture, addressing a critical barrier to their clinical application.