法国巴黎大学Lucie Peduto研究组发现，PDGFRα诱导的基质成熟是抑制产后肠道上皮干性和促进防御机制所需。2022年5月5日出版的《细胞—干细胞》杂志发表了这项成果。

通过在小鼠模型中结合诱导系追踪和转录组学，研究人员确定了一个促分化PDGFRα^high的肠道基质谱系，源自产后LTβR⁺血管周围的基质祖细胞。该谱系的遗传阻断增加了肠道干细胞库，同时减少了断奶期的上皮和免疫成熟度，导致了出生后生长的减少和修复反应的失调。在LTBR基质谱系中敲除PDGFRα，表明PDGFRα对该谱系的命运和功能有重大影响，诱导转录组从前列腺素基因（如Rspo3和Grem1）转向分化因子（包括BMP、维甲酸和层粘连蛋白），并对隐窝内的空间组织和修复反应有影响。

这些结果显示，PDGFRα诱导的肠道基质细胞的转录组转换，需要在出生后的第一周协调出生后肠道的成熟和功能。

据了解，出生后，肠道经历了重大变化，从一个不成熟的增殖状态转变为一个功能性的肠道屏障。

附：英文原文

Title: PDGFRα-induced stromal maturation is required to restrain postnatal intestinal epithelial stemness and promote defense mechanisms

Author: Jean-Marie Jacob, Selene E. Di Carlo, Igor Stzepourginski, Anthony Lepelletier, Papa Diogop Ndiaye, Hugo Varet, Rachel Legendre, Etienne Kornobis, Adam Benabid, Giulia Nigro, Lucie Peduto

Issue&Volume: 2022/05/05

Abstract: 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 PDGFRαHigh 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.

DOI: 10.1016/j.stem.2022.04.005

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00158-8