A classical view of blood cell development is that multipotent hematopoietic stem and progenitor cells (HSPCs) become lineage-restricted at defined stages. Lin⁻c-Kit⁺Sca-1⁺Flt3⁺ cells, termed lymphoid-primed multipotent progenitors (LMPPs), have lost megakaryocyte and erythroid potential but are heterogeneous in their fate. Here, through single-cell RNA sequencing, we identify the expression of Dach1 and associated genes in this fraction as being coexpressed with myeloid/stem genes but inversely correlated with lymphoid genes. Through generation of Dach1–GFP reporter mice, we identify a transcriptionally and functionally unique Dach1–GFP⁻ subpopulation within LMPPs with lymphoid potential with low to negligible classic myeloid potential. We term these ‘lymphoid-primed progenitors’ (LPPs). These findings define an early definitive branch point of lymphoid development in hematopoiesis and a means for prospective isolation of LPPs.

血细胞发育的经典观点是，多能造血干细胞和祖细胞 (HSPC) 在特定阶段成为谱系限制。Lin ^- c-Kit ⁺ Sca-1 ⁺ Flt3 ⁺细胞，称为淋巴引发的多能祖细胞 (LMPP)，已失去巨核细胞和红细胞潜能，但其命运是异质的。在这里，通过单细胞 RNA 测序，我们确定该部分中Dach1和相关基因的表达与骨髓/干基因共表达，但与淋巴基因呈负相关。通过生成Dach1 -GFP 报告小鼠，我们确定了转录和功能上独特的Dach1 -GFP ^-LMPP 内具有淋巴潜能的亚群，经典髓样潜能低至可忽略不计。我们称这些“淋巴引发的祖细胞”（LPP）。这些发现定义了造血中淋巴发育的早期确定分支点，以及前瞻性分离 LPP 的方法。