Hematopoietic stem cells (HSCs) are rare cells that arise in the embryo and sustain adult hematopoiesis. Although the functional potential of nascent HSCs is detectable by transplantation, their native contribution during development is unknown, in part due to the overlapping genesis and marker gene expression with other embryonic blood progenitors. Using single-cell transcriptomics, we define gene signatures that distinguish nascent HSCs from embryonic blood progenitors. Applying a lineage-tracing approach to selectively track HSC output in situ, we find significantly delayed lymphomyeloid contribution. An inducible HSC injury model demonstrates a negligible impact on larval lymphomyelopoiesis following HSC depletion. HSCs are not merely dormant at this developmental stage, as they showed robust regeneration after injury. Combined, our findings illuminate that nascent HSCs self-renew but display differentiation latency, while HSC-independent embryonic progenitors sustain developmental hematopoiesis. Understanding these differences could improve de novo generation and expansion of functional HSCs.

造血干细胞 (HSC) 是在胚胎中产生并维持成人造血功能的稀有细胞。尽管通过移植可以检测到新生 HSC 的功能潜力，但它们在发育过程中的天然贡献是未知的，部分原因是与其他胚胎血祖细胞的重叠起源和标记基因表达。使用单细胞转录组学，我们定义了区分新生 HSC 与胚胎血祖细胞的基因特征。应用血统追踪方法选择性地原位追踪 HSC 输出，我们发现显着延迟的淋巴细胞贡献。诱导型 HSC 损伤模型表明 HSC 耗竭后对幼虫淋巴细胞生成的影响可以忽略不计。HSCs 不仅在这个发育阶段处于休眠状态，因为它们在受伤后表现出强大的再生能力。结合起来，我们的研究结果表明，新生的 HSC 自我更新但显示出分化潜伏期，而 HSC 非依赖性胚胎祖细胞维持发育性造血。了解这些差异可以改善功能性 HSC 的从头生成和扩展。