Stem cells of the oesophageal epithelium

2002 ◽  
Vol 115 (9) ◽  
pp. 1783-1789
Author(s):  
John P. Seery
Keyword(s):  
Stem Cells ◽  
Cell Biology ◽  
Epithelial Stem Cells ◽  
The Past ◽  
The World

Cancers arising in the oesophageal epithelium are among the most common fatal tumors in the world. Despite this, comparatively little is known about the cell biology and organization of this tissue. Recently, in vitro and in vivo techniques developed over the past 30 years for the study of the epidermis have been applied to the study of the oesophageal epithelium. This approach, combined with data from previous histochemical studies, has lead to the identification and isolation of putative oesophageal epithelial stem cells. Oesophageal epithelial stem cells demonstrate several unusual properties, and their identification may facilitate studies on oesophageal carcinogenesis.

The Role of Nucleophosmin In Hematopoietic Stem Cells and the Pathogenesis of Myelodysplastic Syndrome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 95-95 ◽  
Author(s):  
Keisuke Ito ◽  
Paolo Sportoletti ◽  
John G Clohessy ◽  
Grisendi Silvia ◽  
Pier Paolo Pandolfi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Myelodysplastic Syndrome ◽  
Cell Biology ◽  
De Novo ◽  
Stem Cell Biology ◽  
Hematopoietic Stem

Abstract Abstract 95 Myelodysplastic syndrome (MDS) is an incurable stem cell disorder characterized by ineffective hematopoiesis and an increased risk of leukemia transformation. Nucleophosmin (NPM) is directly implicated in primitive hematopoiesis, the pathogenesis of hematopoietic malignancies and more recently of MDS. However, little is known regarding the molecular role and function of NPM in MDS pathogenesis and in stem cell biology. Here we present data demonstrating that NPM plays a critical role in the maintenance of hematopoietic stem cells (HSCs) and the transformation of MDS into leukemia. NPM is located on chromosome 5q and is frequently lost in therapy-related and de novo MDS. We have previously shown that Npm1 acts as a haploinsufficient tumor suppressor in the hematopoietic compartment and Npm1+/− mice develop a hematologic syndrome with features of human MDS, including increased susceptibility to leukemogenesis. As HSCs have been demonstrated to be the target of the primary neoplastic event in MDS, a functional analysis of the HSC compartment is essential to understand the molecular mechanisms in MDS pathogenesis. However, the role of NPM in adult hematopoiesis remains largely unknown as Npm1-deficiency leads to embryonic lethality. To investigate NPM function in adult hematopoiesis, we have generated conditional knockout mice of Npm1, using the Cre-loxP system. Analysis of Npm1 conditional mutants crossed with Mx1-Cre transgenic mice reveals that Npm1 plays a crucial role in adult hematopoiesis and ablation of Npm1 in adult HSCs leads to aberrant cycling and followed by apoptosis. Analysis of cell cycle status revealed that HSCs are impaired in their ability to maintain quiescence after Npm1-deletion and are rapidly depleted in vivo as well as in vitro. Competitive reconstitution assay revealed that Npm1 acts cell-autonomously to maintain HSCs. Conditional inactivation of Npm1 leads to an MDS phenotype including a profoundly impaired ability to differentiate into cells of the erythroid lineage, megakaryocyte dyspoiesis and centrosome amplification. Furthermore, Npm1 loss evokes a p53-dependent response and Npm1-deleted HSCs undergo apoptosis in vivo and in vitro. Strikingly, transfer of the Npm1 mutation into a p53-null background rescued the apoptosis of Npm1-ablated HSCs and resulted in accelerated transformation to an aggressive and lethal form of acute myeloid leukemia. Our findings highlight the crucial role of NPM in stem cell biology and identify a new mechanism by which MDS can progress to leukemia. This has important therapeutic implications for de novo MDS as well as therapy-related MDS, which is known to rapidly evolve to leukemia with frequent loss or mutation of TRP53. Disclosures: No relevant conflicts of interest to declare.

Designing and Engineering Stem Cell Niches

MRS Bulletin ◽  
2010 ◽  
Vol 35 (8) ◽  
pp. 591-596 ◽  
Author(s):  
Ana I. Teixeira ◽  
Ola Hermanson ◽  
Carsten Werner
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Chemical Engineering ◽  
Polyglycolic Acid ◽  
Differentiated Cells ◽  
Extracellular Matrix Components ◽  
Stem Cell Niches

AbstractStem cells have received a lot of attention due to great promises in medical treatment, for example, by replacing lost and sick cells and re-constituting cell populations. There are several classes of stem cells, including embryonic, fetal, and adult tissue specific. More recently, the generation of so-called induced pluripotent stem (iPS) cells from differentiated cells has been established. Common criteria for all types of stem cells include their ability to self-renew and to retain their ability to differentiate in response to specific cues. These characteristics, as well as the instructive steering of the cells into differentiation, are largely dependent on the microenvironment surrounding the cells. Such “stem cell friendly” microenvironments, provided by structural and biochemical components, are often referred to as niches. Biomaterials offer attractive solutions to engineer functional stem cell niches and to steer stem cell state and fatein vitroas well asin vivo. Among materials used so far, promising results have been achieved with low-toxicity and biodegradable polymers, such as polyglycolic acid and related materials, as well as other polymers used as structural “scaffolds” for engineering of extracellular matrix components. To improve the efficiency of stem cell control and the design of the biomaterials, interfaces among stem cell research, developmental biology, regenerative medicine, chemical engineering, and materials research are rapidly developing. Here we provide an introduction to stem cell biology and principles of niche engineering and give an overview of recent advancements in stem cell niche engineering from two stem cell systems—blood and brain.

scholarly journals Platelet-Derived Growth Factor Receptor Alpha as a Marker of Mesenchymal Stem Cells in Development and Stem Cell Biology

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Ramin M. Farahani ◽  
Munira Xaymardan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Growth Factor Receptor ◽  
Stem Cell Marker ◽  
Factor Receptor Alpha ◽  
Lines Of Evidence

Three decades on, the mesenchymal stem cells (MSCs) have been intensively researched on the bench top and used clinically. However, ambiguity still exists in regard to their anatomical locations, identities, functions, and extent of their differentiative abilities. One of the major impediments in the quest of the MSC research has been lack of appropriatein vivomarkers. In recent years, this obstacle has been resolved to some degree as PDGFRαemerges as an important mesenchymal stem cell marker. Accumulating lines of evidence are showing that the PDGFRα+cells reside in the perivascular locations of many adult interstitium and fulfil the classic concepts of MSCsin vitroandin vivo. PDGFRαhas long been recognised for its roles in the mesoderm formation and connective tissue development during the embryogenesis. Current review describes the lines of evidence regarding the role of PDGFRαin morphogenesis and differentiation and its implications for MSC biology.

In vitro and in vivo differentiation of amniotic epithelial stem cells into hepatocyte-like cells

Placenta ◽  
2011 ◽  
Vol 32 ◽  
pp. S336
Author(s):  
F. Marongiu ◽  
R. Gramignoli ◽  
S. Doratiotto ◽  
M. Serra ◽  
M. Sini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Stem Cells ◽  
In Vivo Differentiation

scholarly journals Lactobacillus rhamnosus GG protects the intestinal epithelium from radiation injury through release of lipoteichoic acid, macrophage activation and the migration of mesenchymal stem cells

Gut ◽  
2018 ◽  
Vol 68 (6) ◽  
pp. 1003-1013 ◽  
Author(s):  
Terrence E Riehl ◽  
David Alvarado ◽  
Xueping Ee ◽  
Aaron Zuckerman ◽  
Lynn Foster ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Lamina Propria ◽  
Lactobacillus Rhamnosus ◽  
Lipoteichoic Acid ◽  
Epithelial Stem Cells ◽  
Tlr2 Agonist ◽  
Cox 2

ObjectiveLactobacillus rhamnosus GG (LGG), a probiotic, given by gavage is radioprotective of the mouse intestine. LGG-induced radioprotection is toll-like receptor 2 (TLR2) and cyclooxygenase-2 (COX-2)-dependent and is associated with the migration of COX-2+mesenchymal stem cells (MSCs) from the lamina propria of the villus to the lamina propria near the crypt epithelial stem cells. Our goals were to define the mechanism of LGG radioprotection including identification of the TLR2 agonist, and the mechanism of the MSC migration and to determine the safety and efficacy of this approach in models relevant to clinical radiation therapy.DesignIntestinal radioprotection was modelled in vitro with cell lines and enteroids as well as in vivo by assaying clinical outcomes and crypt survival. Fractionated abdominal and single dose radiation were used along with syngeneic CT26 colon tumour grafts to assess tumour radioprotection.ResultsLGG with a mutation in the processing of lipoteichoic acid (LTA), a TLR2 agonist, was not radioprotective, while LTA agonist and native LGG were. An agonist of CXCR4 blocked LGG-induced MSC migration and LGG-induced radioprotection. LGG given by gavage induced expression of CXCL12, a CXCR4 agonist, in pericryptal macrophages and depletion of macrophages by clodronate liposomes blocked LGG-induced MSC migration and radioprotection. LTA effectively protected the normal intestinal crypt, but not tumours in fractionated radiation regimens.ConclusionsLGG acts as a ‘time-release capsule’ releasing radioprotective LTA. LTA then primes the epithelial stem cell niche to protect epithelial stem cells by triggering a multicellular, adaptive immune signalling cascade involving macrophages and PGE2 secreting MSCs.Trial registration numberNCT01790035; Pre-results.

scholarly journals Transcriptomically-guided mesendoderm induction of human pluripotent stem cells using a systematically defined culture scheme

2019 ◽  
Author(s):  
Richard L Carpenedo ◽  
Sarah Y Kwon ◽  
R Matthew Tanner ◽  
Julien Yockell-Lelièvre ◽  
Chandarong Choey ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cell Biology ◽  
Disease Modeling ◽  
Human Pluripotent Stem Cells ◽  
Endoderm Differentiation ◽  
Prolonged Differentiation ◽  
Defined Culture

SummaryHuman pluripotent stem cells (hPSCs) are an essential cell source in tissue engineering, studies of development, and disease modeling. Efficient, broadly amenable protocols for rapid lineage induction of hPSCs are of great interest in the stem cell biology field. We describe a simple, robust method for differentiation of hPSCs into mesendoderm in defined conditions utilizing single-cell seeding (SCS) and BMP4 and Activin A (BA) treatment. Gene sets and gene ontology terms related to mesoderm and endoderm differentiation were enriched after 48 hours of BA treatment. BA treatment was readily incorporated into existing protocols for chondrogenic and endothelial progenitor cell differentiation. After prolonged differentiation in vitro or in vivo, BA pre-treatment resulted in higher mesoderm and endoderm levels at the expense of ectoderm formation. These data demonstrate that SCS with BA treatment is a powerful method for induction of mesendoderm that can be integrated into protocols for mesoderm and endoderm differentiation.

scholarly journals Hairless is a nuclear receptor corepressor essential for skin function

2009 ◽  
Vol 7 (1) ◽  
pp. nrs.07010 ◽  
Author(s):  
Catherine C. Thompson
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Nuclear Receptors ◽  
Chromatin Remodeling ◽  
Transcriptional Repression ◽  
Critical Role ◽  
Epithelial Stem Cells ◽  
Skin Function

The activity of nuclear receptors is modulated by numerous coregulatory factors. Corepressors can either mediate the ability of nuclear receptors to repress transcription, or can inhibit transactivation by nuclear receptors. As we learn more about the mechanisms of transcriptional repression, the importance of repression by nuclear receptors in development and disease has become clear. The protein encoded by the mammalian Hairless (Hr) gene was shown to be a corepressor by virtue of its functional similarity to the well-established corepressors N-CoR and SMRT. Mutation of the Hr gene results in congenital hair loss in both mice and men. Investigation of Hairless function both in vitro and in mouse models in vivo has revealed a critical role in maintaining skin and hair by regulating the differentiation of epithelial stem cells, as well as a putative role in regulating gene expression via chromatin remodeling.

scholarly journals Bacterial infection drives trained immunity through epigenetic remodeling of epithelial stem cells

2021 ◽  
Author(s):  
Scott Hultgren ◽  
Seongmi Russell ◽  
Hyung Joo Lee ◽  
Benjamin Olson ◽  
Jonathan Livny ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Bacterial Infection ◽  
Bacterial Infections ◽  
Inflammatory Cell ◽  
Host Susceptibility ◽  
Epithelial Stem Cells ◽  
Caspase 1

Abstract Recurrent bacterial infections are a major health burden worldwide, yet the mechanisms dictating host susceptibility to recurrence are poorly understood. Here we demonstrate that an initial bacterial infection of the urinary bladder with uropathogenic E. coli (UPEC) can induce sustained epigenetic changes in the bladder epithelial (urothelial) stem cells that reprogram the differentiated urothelium. We established urothelial stem cell (USC) lines from isogenic mice with different urinary tract infection histories (naïve, chronic or self-resolving). Differentiation of the USC lines in Transwell culture resulted in polarized urothelial cultures that recapitulated distinct remodeling morphologies seen in vivo. In addition, we discovered differences in chromatin accessibility that segregated by disease history, resulting in differences in gene expression upon differentiation of the USC lines in vitro, based on ATAC-seq analysis of the USC lines. Differential basal expression of Caspase-1 led to divergent susceptibilities to inflammatory cell death upon UPEC infection. In mice with a history of chronic infection, enhanced caspase 1-mediated inflammatory cell death was found to be a protective response that enhanced bacterial clearance upon challenge infection. Thus, UPEC infection reshapes the epigenome leading to epithelial-intrinsic remodeling that trains the mucosal immune response to subsequent infection. These findings may have broad implications for the prevention of chronic/recurrent bacterial infections.

scholarly journals Cellular Dynamics of Mouse Trophoblast Stem Cells: Identification of a Persistent Stem Cell Type1

2016 ◽  
Vol 94 (6) ◽  
Author(s):  
Kaori Motomura ◽  
Mami Oikawa ◽  
Michiko Hirose ◽  
Arata Honda ◽  
Sumie Togayachi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Biology ◽  
Expression Profiles ◽  
Single Type ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem ◽  
Differential Expression Pattern

Abstract Mouse trophoblast stem cells (TSCs) proliferate indefinitely in vitro, despite their highly heterogeneous nature. In this study, we sought to characterize TSC colony types by using methods based on cell biology and biochemistry for a better understanding of how TSCs are maintained over multiple passages. Colonies of TSCs could be classified into four major types: type 1 is compact and dome-shaped, type 4 is flattened but with a large multilayered cell cluster, and types 2 and 3 are their intermediates. A time-lapse analysis indicated that type 1 colonies predominantly appeared after passaging, and a single type 1 colony gave rise to all other types. These colony transitions were irreversible, but at least some type 1 colonies persisted throughout culture. The typical cells comprising type 1 colonies were small and highly motile, and they aggregated together to form primary colonies. A hierarchical clustering based on global gene expression profiles suggested that a TSC line containing more type 1 colony cells was similar to in vivo extraembryonic tissues. Among the known TSC genes examined, Elf5 showed a differential expression pattern according to colony type, indicating that this gene might be a reliable marker of undifferentiated TSCs. When aggregated with fertilized embryos, cells from types 1 and 2, but not from type 4, distributed to the polar trophectoderm in blastocysts. These findings indicate that cells typically found in type 1 colonies can persist indefinitely as stem cells and are responsible for the maintenance of TSC lines. They may provide key information for future improvements in the quality of TSC lines.

scholarly journals Chemosensitivity of Patient-Derived Cancer Stem Cells Identifies Colorectal Cancer Patients with Potential Benefit from FGFR Inhibitor Therapy

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2010
Author(s):  
Takehito Yamamoto ◽  
Hiroyuki Miyoshi ◽  
Fumihiko Kakizaki ◽  
Hisatsugu Maekawa ◽  
Tadayoshi Yamaura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Genetic Alterations ◽  
Inhibitor Therapy ◽  
Epithelial Stem Cells ◽  
Colorectal Cancer Patients

Some colorectal cancer patients harboring FGFR (fibroblast growth factor receptor) genetic alterations, such as copy number gain, mutation, and/or mRNA overexpression, were selected for enrollment in several recent clinical trials of FGFR inhibitor, because these genetic alterations were preclinically reported to be associated with FGFR inhibitor sensitivity as well as poor prognosis, invasiveness, and/or metastatic potential. However, few enrolled patients were responsive to FGFR inhibitors. Thus, practical strategies are eagerly awaited that can stratify patients for the subset that potentially responds to FGFR inhibitor chemotherapy. In the present study, we evaluated the sensitivity to FGFR inhibitor erdafitinib on 25 patient-derived tumor-initiating cell (TIC) spheroid lines carrying wild-type RAS and RAF genes, both in vitro and in vivo. Then, we assessed possible correlations between the sensitivity and the genetic/genomic data of the spheroid lines tested. Upon their exposure to erdafitinib, seven lines (7/25, 28%) responded significantly. Normal colonic epithelial stem cells were unaffected by the inhibitors. Moreover, the combination of erdafitinib with EGFR inhibitor erlotinib showed stronger growth inhibition than either drug alone, as efficacy was observed in 21 lines (84%) including 14 (56%) that were insensitive to erdafitinib alone. The in vitro erdafitinib response was accurately reflected on mouse xenografts of TIC spheroid lines. However, we found little correlation between their genetic/genomic alterations of TIC spheroids and the sensitivity to the FGFR inhibitor. Accordingly, we propose that direct testing of the patient-derived spheroids in vitro is one of the most reliable personalized methods in FGFR-inhibitor therapy of colorectal cancer patients.

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