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Single-cell transcriptomic mapping of intestinal epithelium that undergoes 3D morphogenesis and mechanodynamic stimulation in a gut-on-a-chip
- Source :
- iScience, Vol 25, Iss 12, Pp 105521- (2022)
- Publication Year :
- 2022
- Publisher :
- Elsevier, 2022.
-
Abstract
- Summary: The human gut-on-a-chip has demonstrated in vivo-relevant cellular fidelity and physiological functions of Caco-2 intestinal epithelium compared to its static cultures. However, transcriptomic dynamics that controls the morphogenic and mechanodynamic perturbation of Caco-2 epithelium in a microphysiological culture remain elusive. Single-cell transcriptomic analysis revealed that a gut-on-a-chip culture drives three clusters that illustrate distinct gene expressions and their spatial representation in three-dimensional (3D) epithelial layers. A pseudotemporal trajectory analysis elucidated the evolutionary transition from a homogeneous ancestral genotype in Transwell cultures into heterogeneous transcriptomes in gut-on-a-chip cultures, verified in cell cycle perturbation, cytodifferentiation, and intestinal functions in digestion, transport, and drug metabolism. Furthermore, the inversed transcriptomic signature of oncogenes and tumor-suppressor genes of Caco-2 cells confirmed that gut-on-a-chip cultures induce post-mitotic reprogramming of cancer-associated genes. Our study suggests that a physiological gut-on-a-chip culture induces the transcriptomic perturbation of Caco-2 epithelium to elicit in vivo-relevant morphogenesis and restoration of normal physiological functions.
Details
- Language :
- English
- ISSN :
- 25890042
- Volume :
- 25
- Issue :
- 12
- Database :
- Directory of Open Access Journals
- Journal :
- iScience
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.43bb57fd4689456bb5ff92f98db1d683
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.isci.2022.105521