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

A niche-mimetic ex vivo culture (3D-NcadP-Y-UM) preserves long-term repopulating human HSC function while limiting excessive cell cycle activation, enabling serial transplantation.

• Why it matters: Ex vivo HSC expansion often reduces self-renewal and skews output toward myeloid lineages, and the molecular basis of this functional decline is not well defined.
• What they did: Using scMultiome-seq on cord blood CD34+ HSPCs, the study mapped transcriptional/epigenetic changes during culture and then tested a niche-mimetic system with YTHDF2 inhibition (Y13-27), 3D microenvironment, and N-cadherin adhesion, plus UM729.
• The result: Compared with standard culture, 3D-NcadP-Y-UM maintained long-term HSC signatures and multilineage-associated transcription factor motifs while reducing myeloid-associated motif activity and excessive cell cycle activation.

AI summary of the abstract · may contain errors · not medical advice · read the paper.