After birth, the intestine undergoes major changes to shift from an immature proliferative state to a functional intestinal barrier. By combining inducible lineage tracing and transcriptomics in mouse models, we identify a prodifferentiation PDGFRα^High intestinal stromal lineage originating from postnatal LTβR⁺ perivascular stromal progenitors. The genetic blockage of this lineage increased the intestinal stem cell pool while decreasing epithelial and immune maturation at weaning age, leading to reduced postnatal growth and dysregulated repair responses. Ablating PDGFRα in the LTBR stromal lineage demonstrates that PDGFRα has a major impact on the lineage fate and function, inducing a transcriptomic switch from prostemness genes, such as Rspo3 and Grem1, to prodifferentiation factors, including BMPs, retinoic acid, and laminins, and on spatial organization within the crypt-villus and repair responses. Our results show that the PDGFRα-induced transcriptomic switch in intestinal stromal cells is required in the first weeks after birth to coordinate postnatal intestinal maturation and function.

出生后，肠道发生重大变化，从未成熟的增殖状态转变为功能性肠道屏障。通过在小鼠模型中结合诱导型谱系追踪和转录组学，我们确定了源自出生后 LTβR ⁺血管周围基质祖细胞的促分化 PDGFRα^{高肠道基质谱系。}该谱系的遗传阻断增加了肠道干细胞库，同时降低了断奶年龄的上皮和免疫成熟，导致出生后生长减少和修复反应失调。在 LTBR 基质谱系中消融 PDGFRα 表明 PDGFRα 对谱系命运和功能具有重大影响，诱导前干基因（如Rspo3和Grem1，促分化因子，包括 BMP、视黄酸和层粘连蛋白，以及隐窝绒毛内的空间组织和修复反应。我们的研究结果表明，PDGFRα 诱导的肠道基质细胞转录组转换需要在出生后的第一周内协调出生后肠道成熟和功能。