Intestinal Organoid

A special issue of Organoids (ISSN 2674-1172).

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 2561

Special Issue Editor


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Guest Editor
Suntory Foundation for Life Sciences, Bioorganic Research Institute, Kyoto 619-0284, Japan
Interests: intestinal organoid; stem cell; signaling; non-neuronal acetylcholine; acetylcholine receptor
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Special Issue Information

Dear Colleagues,

Intestinal organoids, which were first established in 2009, have emerged as a powerful in vitro tool for studying intestinal biology given their morphological and functional similarity to mature tissues. At present, technological advances in cultured organoids derived from adult-tissue stem cells have allowed for the long-term culture of intestinal stem cells (ISCs) with self-renewal and differentiation potential. Since intestinal organoids are derived from adult stem cells and are composed of multiple cell types, they recapitulate the functionality of the intestinal epithelium. Of note, a single ISC can also generate three-dimensional organoids without any Paneth cells or an ISC niche such as the epithelial niche or stromal niche. The potential to form organoids from crypts is attributed to the presence of ISCs. On the other hand, the intestinal villi consist of fully differentiated cells and hence cannot form organoids. However, the intestinal epithelium can de-differentiate and function as an alternative source of ISCs upon tissue damage and stress conditions such as inflammation and tumorigenesis. In this Special Issue, we elaborate on the advantages of intestinal organoids in different applications, and the key priorities in intestinal organoid engineering for the coming years.

Dr. Toshio Takahashi
Guest Editor

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Keywords

  • intestine
  • organoid
  • crypt
  • villus
  • intestinal epithelium
  • adult stem cell
  • proliferation
  • differentiation
  • cell fate
  • niche

Published Papers (2 papers)

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Research

12 pages, 4377 KiB  
Article
SMAD1 Is Dispensable for CDX2 Induction but Required for the Repression of Ectopic Small-Intestinal Gene Expression in Human-Pluripotent-Stem-Cell-Derived Colonic Organoids
by Na Qu, Abdelkader Daoud, Braxton Jeffcoat and Jorge O. Múnera
Organoids 2023, 2(4), 192-203; https://doi.org/10.3390/organoids2040015 - 14 Nov 2023
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Abstract
The generation of gastrointestinal tissues from human pluripotent stem cells has provided unprecedented insight into the molecular mechanisms that drive the patterning of the primitive gut tube. Previous work has identified bone-morphogenetic-protein (BMP) signaling as an important mediator of mid/hindgut versus foregut and [...] Read more.
The generation of gastrointestinal tissues from human pluripotent stem cells has provided unprecedented insight into the molecular mechanisms that drive the patterning of the primitive gut tube. Previous work has identified bone-morphogenetic-protein (BMP) signaling as an important mediator of mid/hindgut versus foregut and hindgut versus midgut cell fate choice. Inhibition of BMP signaling during gut tube morphogenesis inhibits the expression of the pan-intestinal transcription factor CDX2. Treatment of CDX2+ mid/hindgut cultures with BMP patterns them into hindgut, which gives rise to colonic organoids (HCOs). While the role for BMP signaling is clear, the molecular mechanisms through which BMP signaling patterns the mid/hindgut and colon remain unclear. BMPs bind to BMP receptors, activating a signaling cascade that results in the activation of SMADs, which function as transcription factors. We hypothesized that one of these factors, SMAD1, would be necessary for establishing the CDX2 domain and the colon domain. Unexpectedly, endoderm derived from SMAD1-deficient induced pluripotent stem cells was capable of inducing CDX2 in response to WNT and FGF signaling. In addition, CDX2+ gut tube cultures could activate posterior HOX genes in response to BMP. However, examination of HCOs following cytodifferentiation revealed that SMAD1-deficient HCOs ectopically expressed small-intestinal markers despite expressing posterior HOX genes. These results indicate that there is redundancy of SMADs during early hindgut patterning but that SMAD1 is required for the inhibition of small-intestinal gene expression in HCOs. Full article
(This article belongs to the Special Issue Intestinal Organoid)
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9 pages, 1369 KiB  
Communication
The Intricacies of Inflammatory Bowel Disease: A Preliminary Study of Redox Biology in Intestinal Organoids
by Georg Csukovich, Janina Huainig, Selina Troester, Barbara Pratscher and Iwan Anton Burgener
Organoids 2023, 2(3), 156-164; https://doi.org/10.3390/organoids2030012 - 03 Sep 2023
Cited by 1 | Viewed by 1311
Abstract
We evaluated the redox status, precisely glutathione levels, which have a major impact in cellular detoxification and antioxidant defence in IBD-derived and healthy intestinal organoids. Therefore, we wanted to explore the differences in terms of their redox balance and mitochondrial fitness. To this [...] Read more.
We evaluated the redox status, precisely glutathione levels, which have a major impact in cellular detoxification and antioxidant defence in IBD-derived and healthy intestinal organoids. Therefore, we wanted to explore the differences in terms of their redox balance and mitochondrial fitness. To this end, we introduced a Grx1-roGFP2 construct into the organoids by lentiviral transduction before performing a stress assay by treating the organoids with hydrogen peroxide and examined the GSH/GSSG ratio using confocal imaging. Using ratio imaging, we could detect statistically significant differences between healthy and IBD-derived samples. To gain more insight, we also performed a GSH/GSSG assay, which directly measured glutathione levels. This analysis revealed that both organoid lines had higher levels of oxidized glutathione due to the stress treatment demonstrated by a lower GSH/GSSG ratio compared to the untreated control. Nevertheless, the results showed no significant difference between healthy and IBD-derived organoids. We further challenged organoids with hydrogen peroxide after incubation with MitoTracker® to see if mitochondrial fitness might be different in IBD-derived organoids. However, these results were also very comparable. In summary, our preliminary findings indicate that both organoid lines demonstrate a well-functioning system in terms of analysis but show no clear difference between healthy and IBD-derived samples. Full article
(This article belongs to the Special Issue Intestinal Organoid)
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