Lgr5 marks stem/progenitor cells in ovary and tubal epithelia

Ng, Aik Seng; Tan, Shawna; Singh, Gurmit Singh Naranjan; Rizk, Pamela; Yada, Swathi; Tan, Tuan Zea; Huang, Ruby Yun‐Ju; Leushacke, Marc; Barker, Nick

doi:10.1038/ncb3000

Cited by 202 publications

(225 citation statements)

References 26 publications

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“…Exploiting transgenic mice which allow lineage tracing of cells expressing transcripts from the Lgr5 promoter, it was shown that LGR5-expressing OSE reside predominantly in the hilum, but over time give rise to LGR5 K OSE covering the entire ovary. More recently, Ng et al (2014) have confirmed the utility of LGR5 expression for the identification of putative OSE stem cells; however, in contrast to Fleskin-Niitin et al (2013), LGR5 expressing cells were found not only in the hilum region, but also throughout the surface of the ovary with highest concentrations noted in inter-follicular regions and regions adjacent to ovulatory rupture wounds. Lineage tracing suggested that multiple LGR5 C cells are recruited to effect ovulatory wound repair, and the location of these LGR5 C stem cells at inter-follicular regions may be important for the rapid repair of ovulatory wounds (Ng et al 2014).…”

Section: Somatic Stem Cells Of the Osementioning

confidence: 81%

“…The somatic stem cells in the OSE have been investigated in three distinct contexts: potential stem cells able to regenerate germ cells (Parte et al 2011, Patel et al 2013, Virant-Klun et al 2013a, potential stem cells that give rise to granulosa cells (Hummitzsch et al 2013), and more traditional somatic stem cells whose role is to replenish the OSE following ovulatory wounding (Szotek et al 2008, Motohara et al 2011, Usongo & Farookhi 2012, Auersperg 2013, Flesken-Nikitin et al 2013, Ng et al 2014. While this review focuses briefly on studies that have addressed somatic stem cells that are thought to be required for ovulatory wound repair, the relationship with the HGSEOC of the two former potential stem cell pools cannot be discounted.…”

Section: Somatic Stem Cells Of the Osementioning

confidence: 99%

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Epithelial ovarian cancer stem cells: underlying complexity of a simple paradigm

Garson¹,

Vanderhyden²

2015

Reproduction

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The lack of significant progress in the treatment of epithelial ovarian cancer (EOC) underscores the need to gain a better understanding of the processes that lead to chemoresistance and recurrence. The cancer stem cell (CSC) hypothesis offers an attractive explanation of how a subpopulation of cells within a patient's tumour might remain refractory to treatment and subsequently form the basis of recurrent chemoresistant disease. This review examines the literature defining somatic stem cells of the ovary and fallopian tube, two tissues that give rise to EOC. In addition, considerable research has been reviewed, that has identified subpopulations of EOC cells, based on marker expression (CD133, CD44, CD117, CD24, epithelial cell adhesion molecule, LY6A, ALDH1 and side population (SP)), which are enriched for tumour initiating cells (TICs). While many studies identified either CD133 or CD44 as markers useful for enriching for TICs, there is little consensus. This suggests that EOC cells may have a phenotypic plasticity that may preclude the identification of universal markers defining a CSC. The assay that forms the basis of quantifying TICs is the xenograft assay. Considerable controversy surrounds the xenograft assay and it is essential that some of the potential limitations be examined in this review. Highlighting such limitations or weaknesses is required to properly evaluate data and broaden our interpretation of potential mechanisms that might be contributing to the pathogenesis of ovarian cancer.

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Section: Somatic Stem Cells Of the Osementioning

confidence: 81%

Section: Somatic Stem Cells Of the Osementioning

confidence: 99%

Epithelial ovarian cancer stem cells: underlying complexity of a simple paradigm

Garson¹,

Vanderhyden²

2015

Reproduction

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“…Based on present research, Lgr5 seemed the most likely candidate of these genes to putatively mark the nail stem cells. Functional experiments and genetic lineage analyses have established that Lgr5 is a stem cell marker of both the intestinal epithelium and the hair follicle (17,18), and recent experiments have shown it to mark epithelial stem cells in additional tissues, including the stomach, mammary gland, tongue, and ovary (27)(28)(29)(30). In most of these cases, Lgr5 expression is driven by canonical Wnt signaling, placing Lgr5 in a feed-forward loop to maintain high Wnt signaling within Lgr5-expressing stem cells.…”

Section: Discussionmentioning

confidence: 99%

Lgr6 marks nail stem cells and is required for digit tip regeneration

Lehoczky

Tabin

2015

Proc. Natl. Acad. Sci. U.S.A.

109

128

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The tips of the digits of some mammals, including human infants and mice, are capable of complete regeneration after injury. This process is reliant on the presence of the overlaying nail organ and is mediated by a proliferative blastema. Epithelial Wnt/β-catenin signaling has been shown to be necessary for mouse digit tip regeneration. Here, we report on Lgr5 and Lgr6 (leucine-rich repeat-containing G protein-coupled receptor 5 and 6), two important agonists of the Wnt pathway that are known to be markers of several epithelial stem cell populations. We find that Lgr5 is expressed in a dermal population of cells adjacent to the specialized epithelia surrounding the keratinized nail plate. Moreover, Lgr5-expressing cells contribute to this dermis, but not the blastema, during digit tip regeneration. In contrast, we find that Lgr6 is expressed within cells of the nail matrix portion of the nail epithelium, as well as in a subset of cells in the bone and eccrine sweat glands. Genetic lineage analysis reveals that Lgr6-expressing cells give rise to the nail during homeostatic growth, demonstrating that Lgr6 is a marker of nail stem cells. Moreover, Lgr6-expressing cells contribute to the blastema, suggesting a potential direct role for Lgr6-expressing cells during digit tip regeneration. This role is confirmed by analysis of Lgr6-deficient mice, which have both a nail and bone regeneration defect.

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“…Sophisticated, inducible lineage tracing methods using Cre/loxP transgenic mice are now available that can be used to throw a genetic switch to label a chosen cell population with a fluorescent or histochemical marker that will identify them and all their mitotic progeny. Such methods have been used to trace stem cell lineages in other tissues, including the hair follicle [97] , intestinal epithelium [98][99][100] and ovarian surface epithelium [101] , and this approach could be used to help resolve the LESC vs CESC debate. A similar approach has already been used, in conjunction with a multicoloured reporter construct, to trace clonal lineages in the ocular surface of zebrafish and demonstrate that, as in mice, the initial patchwork of cells established in the embryo is replaced by a radial pattern of clones that extend from the limbus [102] .…”

Section: Lineage Tracing Experimentsmentioning

confidence: 99%

Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance

West¹,

Dora²,

Collinson

2015

WJSC

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In this review we evaluate evidence for three different hypotheses that explain how the corneal epithelium is maintained. The limbal epithelial stem cell (LESC) hypothesis is most widely accepted. This proposes that stem cells in the basal layer of the limbal epithelium, at the periphery of the cornea, maintain themselves and also produce transient (or transit) amplifying cells (TACs). TACs then move centripetally to the centre of the cornea in the basal layer of the corneal epithelium and also replenish cells in the overlying suprabasal layers. The LESCs maintain the corneal epithelium during normal homeostasis and become more active to repair significant wounds. Second, the corneal epithelial stem cell (CESC) hypothesis postulates that, during normal homeostasis, stem cells distributed throughout the basal corneal epithelium, maintain the tissue. According to this hypothesis, LESCs are present in the limbus but are only active during wound healing. We also consider a third possibility, that the corneal epithelium is maintained during normal homeostasis by proliferation of basal corneal epithelial cells without any input from stem cells. After reviewing the published evidence, we conclude that the LESC and CESC hypotheses are consistent with more of the evidence than the third hypothesis, so we do not consider this further. The LESC and CESC hypotheses each have difficulty accounting for one main type of evidence so we evaluate the two key lines of evidence that discriminate between them. Finally, we discuss how lineage-tracing experiments have begun to resolve the debate in favour of the LESC hypothesis. Nevertheless, it also seems likely that some basal corneal epithelial cells can act as long-term progenitors if limbal stem cell function is compromised. Thus, this aspect of the CESC hypothesis may have a lasting impact on our understanding of corneal epithelial maintenance, even if it is eventually shown that stem cells are restricted to the limbus as proposed by the LESC hypothesis.

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Lgr5 marks stem/progenitor cells in ovary and tubal epithelia

Cited by 202 publications

References 26 publications

Epithelial ovarian cancer stem cells: underlying complexity of a simple paradigm

Epithelial ovarian cancer stem cells: underlying complexity of a simple paradigm

Lgr6 marks nail stem cells and is required for digit tip regeneration

Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance

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