Tissue regeneration: Reserve or reverse?

Shivdasani, Ramesh A.; Sauvage, Frédéric J. de

doi:10.1126/science.abb6848

Cited by 54 publications

(39 citation statements)

References 15 publications

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“…A recent study has suggested that under conditions of chemical ablation, the partially differentiated cells of the inner enamel epithelium in the mouse incisor may revert to progenitor cells (Sharir et al, 2019). This idea that tissues can regenerate even if the local stem cell population is almost depleted has been demonstrated in the intestine and other organs (Gola and Fuchs, 2021;Shivdasani et al, 2021).…”

Section: Two Interpretations Of Brdu-labeled Cells -Dedifferentiation Versus Stem/progenitor Cellsmentioning

confidence: 99%

Tooth Removal in the Leopard Gecko and the de novo Formation of Replacement Teeth

et al. 2021

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Many reptiles are able to continuously replace their teeth through life, an ability attributed to the existence of epithelial stem cells. Tooth replacement occurs in a spatially and temporally regulated manner, suggesting the involvement of diffusible factors, potentially over long distances. Here, we locally disrupted tooth replacement in the leopard gecko (Eublepharis macularius) and followed the recovery of the dentition. We looked at the effects on local patterning and functionally tested whether putative epithelial stem cells can give rise to multiple cell types in the enamel organs of new teeth. Second generation teeth with enamel and dentine were removed from adult geckos. The dental lamina was either left intact or disrupted in order to interfere with local patterning cues. The dentition began to reform by 1 month and was nearly recovered by 2–3 months as shown in μCT scans and eruption of teeth labeled with fluorescent markers. Microscopic analysis showed that the dental lamina was fully healed by 1 month. The deepest parts of the dental lamina retained odontogenic identity as shown by PITX2 staining. A pulse-chase was carried out to label cells that were stimulated to enter the cell cycle and then would carry BrdU forward into subsequent tooth generations. Initially we labeled 70–78% of PCNA cells with BrdU. After a 1-month chase, the percentage of BrdU + PCNA labeled cells in the dental lamina had dropped to 10%, consistent with the dilution of the label. There was also a population of single, BrdU-labeled cells present up to 2 months post surgery. These BrdU-labeled cells were almost entirely located in the dental lamina and were the likely progenitor/stem cells because they had not entered the cell cycle. In contrast fragmented BrdU was seen in the PCNA-positive, proliferating enamel organs. Homeostasis and recovery of the gecko dentition was therefore mediated by a stable population of epithelial stem cells in the dental lamina.

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Section: Two Interpretations Of Brdu-labeled Cells -Dedifferentiation Versus Stem/progenitor Cellsmentioning

confidence: 99%

Tooth Removal in the Leopard Gecko and the de novo Formation of Replacement Teeth

et al. 2021

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“…Many types of intestinal cells at intermediate or even terminal differentiation stages can dedifferentiate following a lethal injury in normal tissues to replenish the SC repertoire, or as a consequence of the acquisition of genetic alterations and/or in response to signals from the tumor microenvironment in cancer. Thus, stemness is today considered a modifiable cellular state instead of a permanent feature of a fixed group of normal or cancer cells [ 61 , 62 , 63 ]. Two simultaneous studies using CRISPR-Cas9 to label (with GFP) and then eliminate LGR5 + CSC (by means of knock-in Caspase 9 or diphtheria toxin receptor cassettes) smartly demonstrated the plasticity of human and mouse CRC CSC [ 64 , 65 ].…”

Section: Organoids As a Model To Study Crcmentioning

confidence: 99%

Organoids and Colorectal Cancer

Barbáchano

Fernández‐Barral

Bustamante-Madrid

et al. 2021

Cancers

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Organoids were first established as a three-dimensional cell culture system from mouse small intestine. Subsequent development has made organoids a key system to study many human physiological and pathological processes that affect a variety of tissues and organs. In particular, organoids are becoming very useful tools to dissect colorectal cancer (CRC) by allowing the circumvention of classical problems and limitations, such as the impossibility of long-term culture of normal intestinal epithelial cells and the lack of good animal models for CRC. In this review, we describe the features and current knowledge of intestinal organoids and how they are largely contributing to our better understanding of intestinal cell biology and CRC genetics. Moreover, recent data show that organoids are appropriate systems for antitumoral drug testing and for the personalized treatment of CRC patients.

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“…This is likely enabled by the epigenetic similarities between various crypt populations and ISCs (62, 68), as well as the presence of redundant niche sources (20,21,28,69), which may allow more differentiated types to revert to the stem cell state with relative ease upon encountering the right stimuli. Interestingly, under this model, one could argue that any devoted reserve stem populations would become dispensable; indeed, the most recent studies suggest that de-differentiation (followed by subsequent upregulation of the ISC master regulator Ascl2) can satisfactorily explain intestinal epithelial regeneration upon initial loss of Lgr5+ ISCs (70,71). However, this also constitutes a highly controversial issue, with radioresistant and other potential reserve stem cell populations remaining very possible, as these are not necessarily mutually exclusive models (72,73).…”

Section: Approachesmentioning

confidence: 99%

Cellular origins and lineage relationships of the intestinal epithelium

Capdevila

Trifas

Miller

et al. 2021

American Journal of Physiology-Gastrointestinal and Liver Physi

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Knowledge of the development and hierarchical organization of tissues is key to understanding how they are perturbed in injury and disease, as well as how they may be therapeutically manipulated to restore homeostasis. The rapidly regenerating intestinal epithelium harbors diverse cell types and their lineage relationships have been studied using numerous approaches, from classical label-retaining and genetic lineage tracing methods to novel transcriptome-based annotations. Here, we describe the developmental trajectories that dictate differentiation and lineage specification in the intestinal epithelium. We focus on the most recent single-cell RNA-sequencing (scRNA-seq)-based strategies for understanding intestinal epithelial cell lineage relationships, underscoring how they have refined our view of the development of this tissue and highlighting their advantages and limitations. We emphasize how these technologies have been applied to understand the dynamics of intestinal epithelial cells in homeostatic and injury-induced regeneration models.

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Tissue regeneration: Reserve or reverse?

Abstract: Stem cells recover from injury by tissue dedifferentiation, not from dedicated reserves

Cited by 54 publications

References 15 publications

Tooth Removal in the Leopard Gecko and the de novo Formation of Replacement Teeth

Tooth Removal in the Leopard Gecko and the de novo Formation of Replacement Teeth

Organoids and Colorectal Cancer

Cellular origins and lineage relationships of the intestinal epithelium

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