Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands; Oncode Institute, Hubrecht Institute, 3584 CT Utrecht, the Netherlands.
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands; Oncode Institute, Hubrecht Institute, 3584 CT Utrecht, the Netherlands; Microbiome and Cancer Division, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Cell Rep. 2022 Mar 1;38(9):110438. doi: 10.1016/j.celrep.2022.110438.
Intestinal epithelial cells derive from stem cells at the crypt base and travel along the crypt-villus axis to die at the villus tip. The two dominant villus epithelial cell types, absorptive enterocytes and mucous-secreting goblet cells, are mature when they exit crypts. Murine enterocytes switch functional cell states during migration along the villus. Here, we ask whether this zonation is driven by the bone morphogenetic protein (BMP) gradient, which increases toward the villus. Using human intestinal organoids, we show that BMP signaling controls the expression of zonated genes in enterocytes. We find that goblet cells display similar zonation involving antimicrobial genes. Using an inducible Bmpr1a knockout mouse model, we confirm that BMP controls these zonated genes in vivo. Our findings imply that local manipulation of BMP signal strength may be used to reset the enterocyte "rheostat" of carbohydrate versus lipid uptake and to control the antimicrobial response through goblet cells.
肠上皮细胞来源于隐窝底部的干细胞，并沿着隐窝-绒毛轴移动，最终在绒毛顶端死亡。两种主要的绒毛上皮细胞类型，吸收性肠细胞和分泌黏液的杯状细胞，在离开隐窝时就已经成熟。在沿着绒毛迁移的过程中，小鼠肠细胞会发生功能细胞状态的转变。在这里，我们询问这种分带是否是由向绒毛方向增加的骨形态发生蛋白 (BMP) 梯度驱动的。我们使用人类肠道类器官表明，BMP 信号控制肠细胞中分带基因的表达。我们发现杯状细胞也表现出类似的涉及抗菌基因的分带。使用诱导型 Bmpr1a 基因敲除小鼠模型，我们证实 BMP 在体内控制这些分带基因。我们的研究结果表明，局部操纵 BMP 信号强度可能用于重置肠细胞的“变阻器”，以控制碳水化合物与脂质的摄取，并通过杯状细胞控制抗菌反应。
