Umbilical cord blood (UCB) has had considerable impact in pediatric stem cell transplantation, but its wider use is limited in part by unit size. Long-term ex vivo culture offers one approach to increase engraftment capacity by seeking to expand stem and progenitor cells. Here, we show brief incubation (8 h) of UCB CD34+ cells with the matricellular regulator Nov (CCN3) increases the frequency of serially transplantable hematopoietic stem cells (HSCs) 6-fold. This rapid response suggests recruitment rather than expansion of stem cells; accordingly, in single-cell assays, Nov increases the clonogenicity of phenotypic HSCs without increasing their number through cell division. Recruitment is associated with both metabolic and transcriptional changes, and tracing of cell divisions demonstrates that the increased clonogenic activity resides within the undivided fraction of cells. Harnessing latent stem cell potential through recruitment-based approaches will inform understanding of stem cell state transitions with implications for translation to the clinic.

脐带血 (UCB) 在儿科干细胞移植中产生了相当大的影响，但其更广泛的使用部分受到单位大小的限制。长期离体培养提供了一种通过寻求扩大干细胞和祖细胞来增加移植能力的方法。在这里，我们展示了 UCB CD34+ 细胞与基质细胞调节剂 Nov (CCN3) 的短暂孵育（8 小时）将连续移植的造血干细胞 (HSC) 的频率提高了 6 倍。这种快速反应表明干细胞是招募而不是扩增。因此，在单细胞分析中，Nov 增加了表型 HSC 的克隆形成性，而不会通过细胞分裂增加它们的数量。招募与代谢和转录变化有关，细胞分裂的追踪表明增加的克隆形成活性存在于未分裂的细胞部分中。