Intestinal epithelial stem cells do not protect their genome by asymmetric chromosome segregation

Escobar, Marion; Nicolas, Pierre; Sangar, Fatiha; Laurent‐Chabalier, Sabine; Clair, Philippe; Joubert, Dominique; Jay, Philippe; Legraverend, Catherine

doi:10.1038/ncomms1260

Cited by 62 publications

(58 citation statements)

References 41 publications

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“…It is possible that two stem cell populations co-exist in the gut in an overlapping way, one rapidly cycling and the other slowly cycling and that these may be interconvertable 29,30 . In this regard distinct populations of slow cycling LRCs and more rapidly cycling cells have been previously characterised in both the bulge region of the hair follicle and in the intestine 2,31,32 . In the former case the lgr5-negative cells cells co-exist with lgr5-positive cells in the skin at the lower bulge of the hair follicle and appear to represent an active but heterogenously cycling stem cell pool.…”

Section: Discussionmentioning

confidence: 99%

Identification of Lineage-Uncommitted, Long-Lived, Label-Retaining Cells in Healthy Human Esophagus and Stomach, and in Metaplastic Esophagus

et al. 2013

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Background & Aims:The existence of slowly-cycling, adult stem cells has been challenged by the identification of actively cycling cells. We investigated the existence of uncommitted, slowly cycling cells by tracking 5-iodo-2'-deoxyuridine (IdU) label-retaining cells (LRCs) in normal esophagus, Barrett's esophagus (BE), esophageal dysplasia, adenocarcinoma, and healthy stomach tissues from patients.Methods: Four patients (3 undergoing esophagectomy, 1 undergoing esophageal endoscopic mucosal resection for dysplasia and an esophagectomy for esophageal adenocarcinoma) received intravenous infusion of IdU (200 mg per m 2 body surface area, maximum dose of 400 mg) over a 30-min period; the IdU had a circulation t 1/2 of 8hs. Tissues were collected at 7, 11, 29 and 67 days following infusion, from regions of healthy esophagus, BE, dysplasia, adenocarcinoma, and healthy stomach; they were analyzed by in situ hybridization, flow cytometry, and immunohistochemical analyses. Results:No LRCs were found in dysplasias or adenocarcinomas, but there were significant numbers of LRCs in the base of glands from BE tissue, in the papillae of the basal layer of the esophageal squamous epithelium, and in the neck/isthmus region of healthy stomach. These cells cycled slowly, because IdU was retained for at least 67 days and co-labeling with Ki-67 was infrequent. In glands from BE tissues, most cells did not express defensin-5, Muc-2, or chromogranin A, indicating that they were not lineage committed. Some cells labeled for endocrine markers and IdU at 67 days; these cells represented a small population (<0.1%) of epithelial cells at this timepoint. The epithelial turnover time of the healthy esophageal mucosa was approximately 11 days (twice that of the intestine). Conclusions:LRCs of human esophagus and stomach have many features of stem cells (long lived, slow cycling, uncommitted, and multipotent), and can be found in a recognized stem cell niche. Further analyses of these cells, in healthy and metaplastic epithelia is required.4

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Section: Discussionmentioning

confidence: 99%

Identification of Lineage-Uncommitted, Long-Lived, Label-Retaining Cells in Healthy Human Esophagus and Stomach, and in Metaplastic Esophagus

et al. 2013

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“…This process appears to occur in satellite cells Rocheteau et al, 2012;Shinin et al, 2006), whereas it does not appear to occur in HSCs (Kiel et al, 2007;Wilson et al, 2008). There is disagreement as to whether it occurs in other stem cell populations such as ISCs (Escobar et al, 2011;Falconer et al, 2010;Potten et al, 2002;Schepers et al, 2011), HFSCs (Huh et al, 2011(Huh et al, , 2013Waghmare and Tumbar, 2013), NSCs (Karpowicz et al, 2005) or GSCs (Karpowicz et al, 2009;Yadlapalli and Yamashita, 2013;Yadlapalli et al, 2011) (reviewed in Yennek and Tajbakhsh, 2013).…”

Section: Cell Polarity and Proteostasismentioning

confidence: 99%

When stem cells grow old: phenotypes and mechanisms of stem cell aging

2016

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All multicellular organisms undergo a decline in tissue and organ function as they age. An attractive theory is that a loss in stem cell number and/or activity over time causes this decline. In accordance with this theory, aging phenotypes have been described for stem cells of multiple tissues, including those of the hematopoietic system, intestine, muscle, brain, skin and germline. Here, we discuss recent advances in our understanding of why adult stem cells age and how this aging impacts diseases and lifespan. With this increased understanding, it is feasible to design and test interventions that delay stem cell aging and improve both health and lifespan.

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“…An alternative hypothesis was generated based on early label-retention studies, which relied on [ 3 H]thymidine-labeling followed by long "wash-out" periods to identify relatively slowly dividing, or label retaining cells (LRCs, hypothesized to be stem cells), that were localized mainly to the "ϩ4" position, relative to the base of the crypt (65,66). It remains somewhat controversial if label retention is driven by low rates of proliferation, or by retention of a single DNA template strand in the putative ISC, as conflicting studies have been published (22,68). Unification of the two theories on ISC position has resulted in the general acceptance of two potential ISC populations: an "active", rapidly-cycling ISC population of CBCs, and a "quiescent" LRC or reserve ISC population located at the ϩ4 position (Fig.…”

Section: Identification Of Intestinal Stem and Progenitor Cellsmentioning

confidence: 99%

Defining hierarchies of stemness in the intestine: evidence from biomarkers and regulatory pathways

Gracz

Magness

2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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For decades, the rapid proliferation and welldefined cellular lineages of the small intestinal epithelium have driven an interest in the biology of the intestinal stem cells (ISCs) and progenitors that produce the functional cells of the epithelium. Recent and significant advances in ISC biomarker discovery have established the small intestinal epithelium as a powerful model system for studying general paradigms in somatic stem cell biology and facilitated elegant genetic and functional studies of stemness in the intestine. However, this newfound wealth of ISC biomarkers raises important questions of marker specificity. Furthermore, the ISC field must now begin to reconcile biomarker status with functional stemness, a challenge that is made more complex by emerging evidence that cellular hierarchies in the intestinal epithelium are more plastic than previously imagined, with some progenitor populations capable of dedifferentiating and functioning as ISCs following damage. In this review, we discuss the state of the ISC field in terms of biomarkers, tissue dynamics, and cellular hierarchies, and how these processes might be informed by earlier studies into signaling networks in the small intestine.

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Intestinal epithelial stem cells do not protect their genome by asymmetric chromosome segregation

Cited by 62 publications

References 41 publications

Identification of Lineage-Uncommitted, Long-Lived, Label-Retaining Cells in Healthy Human Esophagus and Stomach, and in Metaplastic Esophagus

Identification of Lineage-Uncommitted, Long-Lived, Label-Retaining Cells in Healthy Human Esophagus and Stomach, and in Metaplastic Esophagus

When stem cells grow old: phenotypes and mechanisms of stem cell aging

Defining hierarchies of stemness in the intestine: evidence from biomarkers and regulatory pathways

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