Integrative multi‐omics analysis of intestinal organoid differentiation. Issue 6 (26th June 2018)

• Record Type: Journal Article
• Authors: Lindeboom, Rik GH; van Voorthuijsen, Lisa; Oost, Koen C; Rodríguez‐Colman, Maria J; Luna‐Velez, Maria V; Furlan, Cristina; Baraille, Floriane; Jansen, Pascal WTC; Ribeiro, Agnès; Burgering, Boudewijn MT; Snippert, Hugo J; Vermeulen, Michiel
• Is Part Of: Molecular systems biology. Volume 14:Issue 6(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-06-26
• Subjects: adult intestinal stem cells -- enterocytes -- Hnf4g -- organoids -- systems biology; Molecular biology -- Periodicals; Systems biology -- Periodicals; 572.8
• DOI: 10.15252/msb.20188227
• Languages: English
• ISSNs: 1744-4292

Abstract

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. Synopsis: An integrative multi‐omics approach reveals global rewiring of gene expression both at the transcript and protein level during intestinal stem cell differentiation. Hepatocyte nuclear factor 4 gamma (Hnf4g) is identified as a major driver of enterocyte differentiation. A multi‐omics framework is applied on stem‐cell‐enriched and ‐depleted mouse intestinal organoids. System wide rewiring of the transcriptome and proteome is observed during intestinal stem cell differentiation. Epigenetic modulation facilitates transcription factor driven differentiation.Hnf4g is identified as a major driver of enterocyte differentiation. Abstract : An integrative multi‐omics approach reveals global rewiring of gene expression both at the transcript and protein level during intestinal stem cell differentiation. Hepatocyte nuclear factor 4 gamma (Hnf4g) is identified as a major driver of enterocyte differentiation.