Spatial discordances between mRNAs and proteins in the intestinal epithelium

Yotam Harnik, Lisa Buchauer, Shani Ben-Moshe, Inna Averbukh, Yishai Levin, Raya Eilam, Andreas E Moor, Shalev Itzkovitz

نتاج البحث: نشر في مجلةمقالةمراجعة النظراء

ملخص

The use of transcriptomes as reliable proxies for cellular proteomes is controversial. In the small intestine, enterocytes operate for 4 days as they migrate along villi, which are highly graded microenvironments. Spatial transcriptomics have demonstrated profound zonation in enterocyte gene expression, but how this variability translates to protein content is unclear. Here we show that enterocyte proteins and messenger RNAs along the villus axis are zonated, yet often spatially discordant. Using spatial sorting with zonated surface markers, together with a Bayesian approach to infer protein translation and degradation rates from the combined spatial profiles, we find that, while many genes exhibit proteins zonated toward the villus tip, mRNA is zonated toward the villus bottom. Finally, we demonstrate that space-independent protein synthesis delays can explain many of the mRNA-protein discordances. Our work provides a proteomic spatial blueprint of the intestinal epithelium, highlighting the importance of protein measurements for inferring cell states in tissues that operate outside of steady state.
اللغة الأصليةالإنجليزيّة
الصفحات (من إلى)1680-1693
عدد الصفحات14
دوريةNature metabolism
مستوى الصوت3
رقم الإصدار12
المعرِّفات الرقمية للأشياء
حالة النشرنُشِر - ديسمبر 2021

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