Developmental Cues and Stage‑Matched Niches for Engineering Engraftable Human HSCs.

Generating functional haematopoietic stem cells (HSCs) from human pluripotent stem cells remains a major goal for both regenerative medicine and the study of early human blood development. Achieving this requires a clear understanding of how HSC identity is established during embryogenesis and how these developmental cues can be recreated in vitro. Recent work from Prof. Hanna Mikkola's group has defined transcriptional signatures and niche interactions that mark the emergence and maturation of human HSCs in vivo. Complementary studies from Professor Elizabeth Ng's team have developed human pluripotent stem cell-based systems that recapitulate key stages of this ontogeny, generating haemogenic endothelium and HSC‑like cells capable of long‑term multilineage engraftment. In this perspective, drawing on the recent ISEH NIC webinar presented by Profs. Mikkola and Ng, we integrate insights from both developmental and engineered systems to outline shared principles of human HSC formation and highlight opportunities to refine in vitro strategies for producing fully functional HSCs. Teaser Abstract What can human development teach us about building haematopoietic stem cells in the laboratory? Inspired by presentations from Profs. Mikkola and Ng at the 2025 ISEH NIC webinar, this perspective highlights the developmental and engineering principles that underpin human HSC formation and considers how these insights are advancing efforts to generate durable, engraftable HSCs for translational and regenerative applications.