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  1. Philip J Smith
  1. Honorary Consultant Gastroenterologist, Department of Gastroenterology, Royal Liverpool Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
  1. Correspondence to Dr Philip J Smith, Honorary Consultant Gastroenterologist, Department of Gastroenterology, Royal Liverpool Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; drphilipjsmithbsg{at}gmail.com

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Spatiotemporally resolved colorectal oncogenesis in mini-colons ex vivo

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The use of organoid cultures has become prevalent in studies attempting to understand intestinal biology and disease. However, such systems have limitations, in particular, modelling of tumours has proved problematic due to cystic structures that do not compare with tissue histology. Here, Lorenzo-Martin et al use a ‘mini-colon’ model that incorporates previously engineered crypt-like structures composed of Matrigel and collagen in a flow-luminal system that reflects the basic intestinal structure. Lorenzo-Martin et al lined these with epithelial cells derived from mice that expressed inducible adenomatous polyposis coli (Apc) loss, Kirsten rat sarcoma virus (Kras) mutations and tumour protein P53 (Tp53) mutations (AKP) when exposed to blue light. Tumours with the triad of mutations developed rapidly compared with cells with single mutations. Crypt and luminal areas (that contain different cell lineages) were then targeted with blue light separately revealed morphological differences in the tumours that subsequently developed cystic-like or dense tumours, respectively, over time. They conclude that different environments shape tumour fate. When cultures were derived from already developed from AKP mice, spatial differences in tumour structure were not observed. Crypt-based tumours were also significantly more proliferative than luminal tumours. Minicolon tumour cultures also reflect both intratumoral and intertumoral heterogeneity as demonstrated by the number of clonal populations derived from light-induced tumours as assessed by single-cell RNAseq (RNA sequencing) that revealed clone-dependent variation of expression of interleukin 1 alpha and cyclin-dependent kinase inhibitor 2A. Minicolons additionally allowed investigation into tumour-related hallmarks and therapeutic interventions that reflect observations in tissue tumours. This article demonstrates the capacity of minicolons to recapitulated intricate, cell-specific, temporal tumour investigations with clinical relevance.

An implantable temperature sensor for the long-term monitoring of intestinal inflammation

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Footnotes

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.