scholarly journals Cell Lineage Tracing Identifies Hormone-Regulated and Wnt-Responsive Vaginal Epithelial Stem Cells

Cell Reports ◽  
2020 ◽  
Vol 30 (5) ◽  
pp. 1463-1477.e7
Author(s):  
Ayesha Ali ◽  
Shafiq M. Syed ◽  
M. Fairuz B. Jamaluddin ◽  
Yolanda Colino-Sanguino ◽  
David Gallego-Ortega ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Lineage ◽  
Lineage Tracing ◽  
Epithelial Stem Cells

scholarly journals Mutations in long-lived epithelial stem cells and their clonal progeny in pre-malignant lesions and in oral squamous cell carcinoma

2020 ◽  
Vol 41 (11) ◽  
pp. 1553-1564
Author(s):  
Marta Melis ◽  
Tuo Zhang ◽  
Theresa Scognamiglio ◽  
Lorraine J Gudas
Keyword(s):  
Stem Cells ◽  
Cell Adhesion ◽  
Squamous Cell ◽  
Planar Cell Polarity ◽  
Molecular Mechanisms ◽  
Growth Factor Receptor ◽  
Lineage Tracing ◽  
Epithelial Stem Cells ◽  
Single Nucleotide Variants ◽  
Phosphoinositide 3 Kinase

Abstract Oral squamous cell carcinomas (OSCCs) are the most common cancers of the oral cavity, but the molecular mechanisms driving OSCC carcinogenesis remain unclear. Our group previously established a murine OSCC model based on a 10-week carcinogen [4-nitroquinoline 1-oxide (4-NQO)] treatment. Here we used K14CreERTAM;Rosa26LacZ mice to perform lineage tracing to delineate the mutational profiles in clonal cell populations resulting from single, long-lived epithelial stem cells, here called LacZ+ stem cell clones (LSCCs). Using laser-capture microdissection, we examined mutational changes in LSCCs immediately after the 10-week 4-NQO treatment and >17 weeks after 4-NQO treatment. We found a 1.8-fold ±0.4 (P = 0.009) increase in single-nucleotide variants and insertions/deletions (indels) in tumor compared with pre-neoplastic LSCCs. The percentages of indels and of loss of heterozygosity events were 1.3-fold±0.3 (P = 0.02) and 2.2-fold±0.7 (P = 0.08) higher in pre-neoplastic compared with tumor LSCCs. Mutations in cell adhesion- and development-associated genes occurred in 83% of the tumor LSCCs. Frequently mutated genes in tumor LSCCs were involved in planar cell polarity (Celsr1, Fat4) or development (Notch1). Chromosomal amplifications in 50% of the tumor LSCCs occurred in epidermal growth factor receptor, phosphoinositide 3-kinase and cell adhesion pathways. All pre-neoplastic and tumor LSCCs were characterized by key smoking-associated changes also observed in human OSCC, C>A and G>T. DeconstructSigs analysis identified smoking and head and neck cancer as the most frequent mutational signatures in pre-neoplastic and tumor LSCCs. Thus, this model recapitulates a smoking-associated mutational profile also observed in humans and illustrates the role of LSCCs in early carcinogenesis and OSCCs.

scholarly journals Breast Cancer Stem Cells: Biomarkers, Identification and Isolation Methods, Regulating Mechanisms, Cellular Origin, and Beyond

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3765
Author(s):  
Xiaoli Zhang ◽  
Kimerly Powell ◽  
Lang Li
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Current Knowledge ◽  
Cell Lineage ◽  
Lineage Tracing ◽  
Breast Cancer Stem Cells ◽  
Full Spectrum ◽  
Cellular Origin ◽  
Treatment Responses

Despite recent advances in diagnosis and treatment, breast cancer (BC) is still a major cause of cancer-related mortality in women. Breast cancer stem cells (BCSCs) are a small but significant subpopulation of heterogeneous breast cancer cells demonstrating strong self-renewal and proliferation properties. Accumulating evidence has proved that BCSCs are the driving force behind BC tumor initiation, progression, metastasis, drug resistance, and recurrence. As a heterogeneous disease, BC contains a full spectrum of different BC subtypes, and different subtypes of BC further exhibit distinct subtypes and proportions of BCSCs, which correspond to different treatment responses and disease-specific outcomes. This review summarized the current knowledge of BCSC biomarkers and their clinical relevance, the methods for the identification and isolation of BCSCs, and the mechanisms regulating BCSCs. We also discussed the cellular origin of BCSCs and the current advances in single-cell lineage tracing and transcriptomics and their potential in identifying the origin and lineage development of BCSCs.

scholarly journals Fibroblast growth factor receptor-3 regulates Paneth cell lineage allocation and accrual of epithelial stem cells during murine intestinal development

2009 ◽  
Vol 297 (1) ◽  
pp. G168-G178 ◽  
Author(s):  
Alda Vidrich ◽  
Jenny M. Buzan ◽  
Brooks Brodrick ◽  
Chibuzo Ilo ◽  
Leigh Bradley ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Paneth Cell ◽  
Cell Lineage ◽  
Growth Factor Receptor ◽  
Intestinal Development ◽  
Fibroblast Growth ◽  
Epithelial Stem Cells

Fibroblast growth factor receptor 3 (FGFR-3) is expressed in the lower crypt epithelium, where stem cells of the intestine reside. The role of FGFR-3 signaling in regulating features of intestinal morphogenesis was examined in FGFR-3-null (FGFR-3−/−) mice. FGFR-3−/− mice had only about half the number of intestinal crypts and a marked decrease in the number of functional clonogenic stem cells, as assessed by an in vivo microcolony-forming assay, compared with wild-type littermates. A marked deficit in allocation of progenitor cells to Paneth cell differentiation was noted, although all the principal epithelial lineages were represented in FGFR-3−/− mice. The total cellular content and nuclear localization of β-catenin protein were reduced in FGFR-3−/− mice, as was expression of cyclin D1 and matrix metalloproteinase-7, major downstream targets of β-catenin/T cell factor-4 (Tcf-4) signaling. Activation of FGFR-3 in Caco-2 cells, an intestinal epithelial cell line, abrogated the fall in β-catenin/Tcf-4 signaling activity that is normally observed in these cells as cultures become progressively more confluent. These findings are consistent with the hypothesis that, during intestinal development, FGFR-3 signaling regulates crypt epithelial stem cell expansion and crypt morphogenesis, as well as Paneth cell lineage specification, through β-catenin/Tcf-4-dependent and -independent pathways.

scholarly journals Tracing epithelial stem cells during development, homeostasis, and repair

2012 ◽  
Vol 197 (5) ◽  
pp. 575-584 ◽  
Author(s):  
Alexandra Van Keymeulen ◽  
Cédric Blanpain
Keyword(s):  
Stem Cells ◽  
Tissue Regeneration ◽  
External Environment ◽  
Lineage Tracing ◽  
The Body ◽  
Genetic Lineage ◽  
Epithelial Stem Cells ◽  
Differentiation Potential ◽  
Physiological Conditions ◽  
Genetic Lineage Tracing

Epithelia ensure many critical functions of the body, including protection against the external environment, nutrition, respiration, and reproduction. Stem cells (SCs) located in the various epithelia ensure the homeostasis and repair of these tissues throughout the lifetime of the animal. Genetic lineage tracing in mice has allowed the labeling of SCs and their progeny. This technique has been instrumental in characterizing the origin and heterogeneity of epithelial SCs, their tissue location, and their differentiation potential under physiological conditions and during tissue regeneration.

scholarly journals Localization of Putative Stem Cells in Dental Epithelium and Their Association with Notch and Fgf Signaling

1999 ◽  
Vol 147 (1) ◽  
pp. 105-120 ◽  
Author(s):  
Hidemitsu Harada ◽  
Päivi Kettunen ◽  
Han-Sung Jung ◽  
Tuija Mustonen ◽  
Y. Alan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Cell Lineage ◽  
Fgf Signaling ◽  
Epithelial Stem Cells ◽  
Lunatic Fringe ◽  
Reticulum Cells ◽  
Stellate Reticulum ◽  
Mouse Incisor ◽  
Basal Epithelial Cells

The continuously growing mouse incisor is an excellent model to analyze the mechanisms for stem cell lineage. We designed an organ culture method for the apical end of the incisor and analyzed the epithelial cell lineage by 5-bromo-2′-deoxyuridine and DiI labeling. Our results indicate that stem cells reside in the cervical loop epithelium consisting of a central core of stellate reticulum cells surrounded by a layer of basal epithelial cells, and that they give rise to transit-amplifying progeny differentiating into enamel forming ameloblasts. We identified slowly dividing cells among the Notch1-expressing stellate reticulum cells in specific locations near the basal epithelial cells expressing lunatic fringe, a secretory molecule modulating Notch signaling. It is known from tissue recombination studies that in the mouse incisor the mesenchyme regulates the continuous growth of epithelium. Expression of Fgf-3 and Fgf-10 were restricted to the mesenchyme underlying the basal epithelial cells and the transit-amplifying cells expressing their receptors Fgfr1b and Fgfr2b. When FGF-10 protein was applied with beads on the cultured cervical loop epithelium it stimulated cell proliferation as well as expression of lunatic fringe. We present a model in which FGF signaling from the mesenchyme regulates the Notch pathway in dental epithelial stem cells via stimulation of lunatic fringe expression and, thereby, has a central role in coupling the mitogenesis and fate decision of stem cells.

scholarly journals Bipotent stem cells support the cyclical regeneration of endometrial epithelium of the murine uterus

2019 ◽  
Vol 116 (14) ◽  
pp. 6848-6857 ◽  
Author(s):  
Shiying Jin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Population ◽  
Lineage Tracing ◽  
Tissue Loss ◽  
Stem Cell Population ◽  
Epithelial Stem Cells ◽  
Mouse Uterus ◽  
Epithelial Regeneration ◽  
Endometrial Epithelium

The endometrial epithelium of the uterus regenerates periodically. The cellular source of newly regenerated endometrial epithelia during a mouse estrous cycle or a human menstrual cycle is presently unknown. Here, I have used single-cell lineage tracing in the whole mouse uterus to demonstrate that epithelial stem cells exist in the mouse uterus. These uterine epithelial stem cells provide a resident cellular supply that fuels endometrial epithelial regeneration. They are able to survive cyclical uterine tissue loss and persistently generate all endometrial epithelial lineages, including the functionally distinct luminal and glandular epithelia, to maintain uterine cycling. The uterine epithelial stem cell population also supports the regeneration of uterine endometrial epithelium post parturition. The 5-ethynyl-2′-deoxyuridine pulse-chase experiments further reveal that this stem cell population may reside in the intersection zone between luminal and glandular epithelial compartments. This tissue distribution allows these bipotent uterine epithelial stem cells to bidirectionally differentiate to maintain homeostasis and regeneration of mouse endometrial epithelium under physiological conditions. Thus, uterine function over the reproductive lifespan of a mouse relies on stem cell-maintained rhythmic endometrial regeneration.

Multipotential stem cells in adult mouse gastric epithelium

2002 ◽  
Vol 283 (3) ◽  
pp. G767-G777 ◽  
Author(s):  
Matthew Bjerknes ◽  
Hazel Cheng
Keyword(s):  
Stem Cells ◽  
Adult Mouse ◽  
Cell Lineage ◽  
Cell Types ◽  
Lineage Tracing ◽  
Gastric Epithelium ◽  
Chemical Mutagenesis ◽  
Cell Type ◽  
Mature Cell ◽  
Mature Cell Type

Previous studies of chimeric animals demonstrate that multipotential stem cells play a role in the development of the gastric epithelium; however, despite much effort, it is not clear whether they persist into adulthood. Here, chemical mutagenesis was used to label random epithelial cells by loss of transgene function in adult hemizygous ROSA26 mice, a mouse strain expressing the transgene lacZ in all tissues. Many clones derived from such cells contained all the major epithelial cell types, thereby demonstrating existence of functional multipotential stem cells in adult mouse gastric epithelium. We also observed clones containing only a single mature cell type, indicating the presence of long-lived committed progenitors in the gastric epithelium. Similar results were obtained in duodenum and colon, showing that this mouse model is suitable for lineage tracing in all regions of the gastrointestinal tract and likely useful for cell lineage studies in other adult renewing tissues.

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