The transcriptional repressor Blimp1/Prdm1 regulates postnatal reprogramming of intestinal enterocytes

被引:117
作者
Harper, James [1 ]
Mould, Arne [1 ]
Andrews, Robert M. [2 ]
Bikoff, Elizabeth K. [1 ]
Robertson, Elizabeth J. [1 ]
机构
[1] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
[2] Wellcome Trust Sanger Inst, Hinxton Cambridge CB10 1SA, England
基金
英国惠康基金;
关键词
enterocyte maturation; gut development; nutrition; cell fate; TERMINAL DIFFERENTIATION; TARGET GENES; PANETH CELLS; MOUSE; BLIMP-1; PROTEIN; EXPRESSION; MATURATION; MICE; LOCALIZATION;
D O I
10.1073/pnas.1105852108
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Female mammals produce milk to feed their newborn offspring before teeth develop and permit the consumption of solid food. Intestinal enterocytes dramatically alter their biochemical signature during the suckling-to-weaning transition. The transcriptional repressor Blimp1 is strongly expressed in immature enterocytes in utero, but these are gradually replaced by Blimp1(-) crypt-derived adult enterocytes. Here we used a conditional inactivation strategy to eliminate Blimp1 function in the developing intestinal epithelium. There was no noticeable effect on gross morphology or formation of mature cell types before birth. However, survival of mutant neonates was severely compromised. Transcriptional profiling experiments reveal global changes in gene expression patterns. Key components of the adult enterocyte biochemical signature were substantially and prematurely activated. In contrast, those required for processing maternal milk were markedly reduced. Thus, we conclude Blimp1 governs the developmental switch responsible for postnatal intestinal maturation.
引用
收藏
页码:10585 / 10590
页数:6
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