Tracing epithelial stem cells during development, homeostasis, and repair

Keymeulen, Alexandra Van; Blanpain, Cédric

doi:10.1084/jem2096oia12

Cited by 16 publications

(21 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, there is increasing evidence that normal tissue stem cells that are identified by their tissue-regenerative activity in different assays may fail to include cells with similar latent potentialities that are only revealed under different conditions. Examples of this situation have recently been documented for several epithelial tissues in the mouse, including the skin, mammary gland and intestine 21 . Memory T and B lymphocytes also represent anomalous differentiated cells that seem to have a very extensive innate self-renewal ability.…”

Section: Csc Definitions and Terminologymentioning

confidence: 97%

“…This paradigm was first established in the haematopoietic system in mice and humans and has since been extended to many other tissues in both species 3 . Interestingly, it has also become apparent that even stringently defined normal tissue stem cells with extensive self-renewal properties can be intrinsically heterogeneous with regard to their differentiation and selfrenewal control in different sites or stages of development [19][20][21] . Thus, heterogeneity among CSCs in a single tumour type, or even within a single tumour, cannot be assumed to be indicative of an abnormal (tumour-specific) process or to be a consequence of a DNA mutation.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Cancer stem cell definitions and terminology: the devil is in the details

Valent

Bonnet

Maria³

et al. 2012

Nat Rev Cancer

625

564

View full text Add to dashboard Cite

| The cancer stem cell (CSC) concept has important therapeutic implications, but its investigation has been hampered both by a lack of consistency in the terms used for these cells and by how they are defined. Evidence of their heterogeneous origins, frequencies and their genomic, as well as their phenotypic and functional, properties has added to the confusion and has fuelled new ideas and controversies. Participants in The Year 2011 Working Conference on CSCs met to review these issues and to propose a conceptual and practical framework for CSC terminology. More precise reporting of the parameters that are used to identify CSCs and to attribute responses to them is also recommended as key to accelerating an understanding of their biology and developing more effective methods for their eradication in patients. PERSPECTIVES NATURE REVIEWS | CANCER VOLUME 12 | NOVEMBER 2012 | 767

show abstract

Section: Csc Definitions and Terminologymentioning

confidence: 97%

mentioning

confidence: 99%

Cancer stem cell definitions and terminology: the devil is in the details

Valent

Bonnet

Maria³

et al. 2012

Nat Rev Cancer

625

564

View full text Add to dashboard Cite

show abstract

“…The departure of theory from experiment at clone sizes of 0.05 mm 2 and below indicates the resolution limit of the sequencing approach. With a basal cell density of 10,000 cells per mm 2 , this suggests that a resolution limit of around 500 basal cells. Error bars denote SEM.…”

Section: Nonneutral Expansion Of Rare Mutant Clonesmentioning

confidence: 99%

“…stem cells | DNA sequencing | epidermis | cancer A dvances in genetic lineage tracing in transgenic animal models have provided important insights into the proliferative potential and fate behavior of stem and progenitor cell populations in normal tissues (1,2). As well as providing constraints on the mechanisms that regulate stem cell self-renewal, these approaches have established a quantitative framework to address tumor initiation and progression (3)(4)(5)(6).…”

mentioning

confidence: 99%

Deep sequencing as a probe of normal stem cell fate and preneoplasia in human epidermis

Simons

2015

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

View full text Add to dashboard Cite

Using deep sequencing technology, methods based on the sporadic acquisition of somatic DNA mutations in human tissues have been used to trace the clonal evolution of progenitor cells in diseased states. However, the potential of these approaches to explore cell fate behavior of normal tissues and the initiation of preneoplasia remain underexploited. Focusing on the results of a recent deep sequencing study of eyelid epidermis, we show that the quantitative analysis of mutant clone size provides a general method to resolve the pattern of normal stem cell fate and to detect and characterize the mutational signature of rare field transformations in human tissues, with implications for the early detection of preneoplasia.stem cells | DNA sequencing | epidermis | cancer A dvances in genetic lineage tracing in transgenic animal models have provided important insights into the proliferative potential and fate behavior of stem and progenitor cell populations in normal tissues (1, 2). As well as providing constraints on the mechanisms that regulate stem cell self-renewal, these approaches have established a quantitative framework to address tumor initiation and progression (3-6). However, studies based on the clonal activation of oncogenes in animal models can fail to recapitulate the natural processes that lead to neoplasia in human tissues. In recent years, there has been increasing emphasis on the characterization of cancer genomes in human tissues and their potential to elucidate the pathways involved in tumor progression (7)(8)(9)(10)(11)(12)(13)(14). Although these studies have revealed a range of cancer genes (15), the heterogeneity and evolutionary diversity of the tumor environment make the separation of driver and passenger mutations challenging.Against the trend to focus on human tumor samples, a recent study has used ultradeep exome sequencing to determine the mutational profile of normal human eyelid epidermis (16). In the course of DNA replication, all dividing cells are subject to random SNPs. If the mutation rate is sufficiently low that their acquisition at a given locus in a cell subpopulation is typically associated with a single event, they confer a potentially unique hereditary label on cells, allowing the fate of their progeny to be traced over time. By resolving the mutant allele fraction in a biopsy using deep sequencing, the relative size of mutant clones can be inferred. A similar approach based on the spontaneous acquisition of mitochondrial DNA mutation has been used to address progenitor cell fate in human airways and intestinal epithelia (17,18). To assess the selective growth advantage of different mutations in normal epidermis, Martincorena et al. (16) compared the dN/dS ratio and average size of clones derived from mutations in genes associated with cancer drivers with those associated with synonymous mutations in nondriver genes. Their analysis showed a significant increase in the abundance and average size of clones that bear mutations in NOTCH1 and tumor protein p53 (TP53) compared wit...

show abstract

“…7B,C). Although our immunofluorescence and qPCR analyses in multiple models support the idea of differentiation of MaSCs towards luminal lineages, mammary lineage tracing in Cbl flox / Cbl-b flox mice bearing the dual reporter, possibly using K14-Cre (Van Keymeulen and Blanpain, 2012;Visvader and Stingl, 2014), will be needed to definitively test this idea.…”

Section: Discussionmentioning

confidence: 87%