Adult gastric stem cells and their niches

Bartfeld, Sina; Koo, Bon–Kyoung

doi:10.1002/wdev.261

Cited by 35 publications

(18 citation statements)

References 71 publications

(190 reference statements)

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“…To determine the significance of these Wnt secreting stromal cells as a stem cell niche, we conditionally deleted Wntless (Wls), a transmembrane protein essential for the secretion of lipid modified Endothelial cells Stromal cells_Rbp7 high Stromal cells_Sfrp2 high Pericyte-like stromal cells Endothelial cells_Selp high Stromal cells_Sorbs2 high Lymphatic endothelial cells Stromal cells_Fmo2 high 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Stromal cells_Ces1d Macrophage-like cells_Cd74_high Wnts 28 . The isthmus of antral gastric glands, where Lgr5 is expressed has been also proposed as a potential Wnt niche 10,23,29,30 . Wnt signaling is known to promote intestinal secretory lineage differentiation [31][32][33] .…”

Section: Resultsmentioning

confidence: 99%

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Single cell and genetic analyses reveal conserved populations and signaling mechanisms of gastrointestinal stromal niches

et al. 2020

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Stomach and intestinal stem cells are located in discrete niches called the isthmus and crypt, respectively. Recent studies have demonstrated a surprisingly conserved role for Wnt signaling in gastrointestinal development. Although intestinal stromal cells secrete Wnt ligands to promote stem cell renewal, the source of stomach Wnt ligands is still unclear. Here, by performing single cell analysis, we identify gastrointestinal stromal cell populations with transcriptome signatures that are conserved between the stomach and intestine. In close proximity to epithelial cells, these perictye-like cells highly express telocyte and pericyte markers as well as Wnt ligands, and they are enriched for Hh signaling. By analyzing mice activated for Hh signaling, we show a conserved mechanism of GLI2 activation of Wnt ligands. Moreover, genetic inhibition of Wnt secretion in perictye-like stromal cells or stromal cells more broadly demonstrates their essential roles in gastrointestinal regeneration and development, respectively, highlighting a redundancy in gastrointestinal stem cell niches.

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Section: Resultsmentioning

confidence: 99%

“…Although thought to be restricted to the intestine and suppressed in the stomach 4,8 , Wnt signaling has recently been shown to perform a surprisingly conserved function in stomach stem cells and their development 9 . However, how and where Wnt ligands in the stomach are produced is unknown 10 .…”

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confidence: 99%

Single cell and genetic analyses reveal conserved populations and signaling mechanisms of gastrointestinal stromal niches

et al. 2020

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“…This process is regulated by multipotent stem cells, which give rise to all gastrointestinal epithelial cell lineages and can regenerate whole intestinal crypts and gastric glands. The stem cells of the gastrointestinal tract are yet undefined, although it is generally agreed that they are located within a ‘niche’ in the intestinal crypts and gastric glands [114]: Two niches seem to co-exist in the gastric unit: one in the isthmus region and the other at the base of the gland, although the precise features of the cell populations and the two niches are currently under debate [115]. The current evidence suggests that gastric stem cells in every gastric gland give rise to four functionally distinct cell lineages: parietal, surface mucous (pit), zymogenic, and enteroendocrine.Nearly 90% of the intestinal epithelium is replaced every 3–4 days by cells newly generated from the crypt epithelium; however, long-lived intestinal stem cells (ISCs) are harboured in the crypt bottom interdigitated between Paneth cells, where cells are physically shielded from the content of the lumen [116].…”

Section: Stem Cell Niches In Adult Tissuesmentioning

confidence: 99%

Relevance of Oxygen Concentration in Stem Cell Culture for Regenerative Medicine

Mas-Bargues

Sanz-Ros

Román-Domínguez

et al. 2019

IJMS

169

108

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The key hallmark of stem cells is their ability to self-renew while keeping a differentiation potential. Intrinsic and extrinsic cell factors may contribute to a decline in these stem cell properties, and this is of the most importance when culturing them. One of these factors is oxygen concentration, which has been closely linked to the maintenance of stemness. The widely used environmental 21% O2 concentration represents a hyperoxic non-physiological condition, which can impair stem cell behaviour by many mechanisms. The goal of this review is to understand these mechanisms underlying the oxygen signalling pathways and their negatively-associated consequences. This may provide a rationale for culturing stem cells under physiological oxygen concentration for stem cell therapy success, in the field of tissue engineering and regenerative medicine.

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“…Adult stem cells are thought to live in a specific niche of each tissue, where they are dividing and creating new cells only when the body needs more cells. For instance: intestinal stem cells reside at the crypt base and give rise to all cell types found within the crypt (31). These findings raise the possibility that the niche itself determines the cell stemness state and not an initially coded cell fate: the ability of cells to go through numerous cycles of cell division while maintaining the undifferentiated state (selfrenewal) is only the consequence of their localization in the "stem cell niche", i.e.…”

Section: Discussionmentioning

confidence: 99%

Biological noise and positional effects influence cell stemness

Blum

Henzi

Schwaller

et al. 2018

Journal of Biological Chemistry

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Biological (or cellular) noise is the random quantitative variability of proteins and other molecules in individual, genetically identical cells. As the result of biological noise in the levels of some transcription factors that determine a cell's differentiation status, differentiated cells may dedifferentiate to a stem cell state given a sufficiently long time period. Here, to provide direct evidence supporting this hypothesis, we used a live-cell monitoring system based on eGFP expression to continuously assess the "stemness" of individual human and murine malignant mesothelioma (MM) cells over a period of up to 3 months. Re-expression of the transcription factors, the top hierarchical stemness markers SRY-box 2 (Sox2) and octamer-binding transcription factor (Oct4), monitored as cells' eGFP expression was observed in a subpopulation of differentiated eGFP(-) MM cells. However, we found that this transition was extremely rare. Of note, when it did occur, neighboring cells that were not direct descendants of a newly emerged eGFP(+) stem cell were more likely than non-neighboring cells to also become an eGFP(+) stem cell. This observation suggested a positional effect and led to a clustered "mosaic" reappearance of eGFP(+) stem cells. Moreover, stem cells reappeared even in cell cultures derived from one single differentiated eGFP(-) cell. On the basis of our experimental in vitro and in vivo findings, we developed a tumor growth model to predict the clustered localization of cancer stem cells within a tumor mass.Regarding the heterogeneity with respect to differentiation, cancer cell populations consist of cancer stem cells (CSC) and a majority of non-CSC or 'bulk' cancer cells. It is hypothesized that essentially the CSC subpopulation possesses the capability of tumor initiation and has the capacity for self-renewal (1,2). Two main theories were initially developed to explain the distribution of CSC within a tumor: the hierarchical and the stochastic model (1). The hierarchical model suggests that the pool of CSC can only be maintained by cells that have CSC characteristics and by definition, the ability to give rise to progeny with unlimited proliferative capacity. Thus, tumors contain: I) proliferating CSC that The cells in such a tumor do not operate in a deterministic, "well-organized" system -any cell has the same intrinsic potential to contribute to tumor growth. Unlike in the hierarchical model, the stochastic model predicts that CSC are not necessarily and exclusively derived from the CSC cell population. Currently, there is no definitive proof in favor of either model of tumor growth. The development of different cancer types may be explained in different ways; leukemia are thought to mostly follow the hierarchical model (3), while breast cancers likely develop according to the stochastic approach (4).Malignant mesotheliomas (MM) are tumors originating from the serosal cells covering the pleural, peritoneal or pericardial cavities. MM are highly aggressive neoplasms most often associated with...

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Adult gastric stem cells and their niches

Cited by 35 publications

References 71 publications

Single cell and genetic analyses reveal conserved populations and signaling mechanisms of gastrointestinal stromal niches

Single cell and genetic analyses reveal conserved populations and signaling mechanisms of gastrointestinal stromal niches

Relevance of Oxygen Concentration in Stem Cell Culture for Regenerative Medicine

Biological noise and positional effects influence cell stemness

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