Integrative multi-omics analysis of intestinal organoid differentiation.
Mol Syst Biol
; 14(6): e8227, 2018 06 26.
Article
en En
| MEDLINE
| ID: mdl-29945941
ABSTRACT
Intestinal organoids accurately recapitulate epithelial homeostasis in vivo, thereby representing a powerful in vitro system to investigate lineage specification and cellular differentiation. Here, we applied a multi-omics framework on stem cell-enriched and stem cell-depleted mouse intestinal organoids to obtain a holistic view of the molecular mechanisms that drive differential gene expression during adult intestinal stem cell differentiation. Our data revealed a global rewiring of the transcriptome and proteome between intestinal stem cells and enterocytes, with the majority of dynamic protein expression being transcription-driven. Integrating absolute mRNA and protein copy numbers revealed post-transcriptional regulation of gene expression. Probing the epigenetic landscape identified a large number of cell-type-specific regulatory elements, which revealed Hnf4g as a major driver of enterocyte differentiation. In summary, by applying an integrative systems biology approach, we uncovered multiple layers of gene expression regulation, which contribute to lineage specification and plasticity of the mouse small intestinal epithelium.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Organoides
/
Biología Computacional
/
Organogénesis
/
Intestinos
Límite:
Animals
Idioma:
En
Revista:
Mol Syst Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOTECNOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Países Bajos