Spatial discordances between mRNAs and proteins in the intestinal epithelium.
Nat Metab
; 3(12): 1680-1693, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-34931081
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
/
Proteoma
/
Transcriptoma
/
Mucosa Intestinal
Limite:
Animals
Idioma:
En
Revista:
Nat Metab
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Israel