scholarly journals Identification and Characterization of Stem Cells in Mammalian Esophageal Stratified Squamous Epithelia

2021 ◽  
Author(s):  
Yanan Yang ◽  
Guodong Deng ◽  
Lili Qiao ◽  
Hui Yuan ◽  
Xiaohong Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Wnt Signaling ◽  
Squamous Epithelium ◽  
Formation Rate ◽  
Basal Layer ◽  
Stem Cell Population ◽  
Basal Cells ◽  
Esophageal Epithelium ◽  
Low Levels

Somatic stem cells are essential for maintenance of cell proliferation-differentiation homeostasis in organs. Despite the importance, how the esophageal epithelium that executes its self-renewal and maintenance remains elusive. In this study, using 5-bromo-2'-deoxyuridine (BrdU) label-chase in rat and rat esophageal keratinocyte cell line-derived organoids together with genome-wide DNA methylation profiling and single-cell RNA sequencing (scRNA-seq), we identify slow cycling/quiescent stem cell population that contain high levels of hemidesmosome (HD)’s and low levels of Wnt signaling localized spatially and randomly at the basal layer of the esophageal epithelium. Pseudo-time cell trajectory from scRNA-seq indicates that cell fates begin from quiescent basal cells (the stem cells) of the basal layer that produce proliferating and/or differentiating cells in the basal layer, which, in turn, progress into differentiating cells in the suprabasal layer, ultimately transforming into differentiated keratinocytes in the differentiated layer. Perturbations of HD component expressions and/or Wnt signaling reduce stem cell in the basal layer of esophageal keratinocyte organoids, resulting in alterations of organoid formation rate, size, morphogenesis and proliferation-differentiation homeostasis. Furthermore, we show that not only high levels of HDs and low levels of Wnt signaling but also an interplay between HD and Wnt signaling defined stem cells of the basal layer in the esophageal squamous epithelium. Hence, HDs and Wnt signaling are the critical determinants for defining stem cells of the basal layer required for proliferation-differentiation homeostasis and maintenance in the mammalian esophageal squamous epithelium.

scholarly journals Transcription factor p63 controls the reserve status but not the stemness of horizontal basal cells in the olfactory epithelium

2015 ◽  
Vol 112 (36) ◽  
pp. E5068-E5077 ◽  
Author(s):  
Nikolai Schnittke ◽  
Daniel B. Herrick ◽  
Brian Lin ◽  
Jesse Peterson ◽  
Julie H. Coleman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Olfactory Epithelium ◽  
Tissue Injury ◽  
Cell Types ◽  
Stem Cell Population ◽  
Basal Cells ◽  
Loss Of Function ◽  
Down Regulation ◽  
Horizontal Basal Cells

Adult tissue stem cells can serve two broad functions: to participate actively in the maintenance and regeneration of a tissue or to wait in reserve and participate only when activated from a dormant state. The adult olfactory epithelium, a site for ongoing, life-long, robust neurogenesis, contains both of these functional stem cell types. Globose basal cells (GBCs) act as the active stem cell population and can give rise to all the differentiated cells found in the normal tissue. Horizontal basal cells (HBCs) act as reserve stem cells and remain dormant unless activated by tissue injury. Here we show that HBC activation following injury by the olfactotoxic gas methyl bromide is coincident with the down-regulation of protein 63 (p63) but anticipates HBC proliferation. Gain- and loss-of-function studies show that this down-regulation of p63 is necessary and sufficient for HBC activation. Moreover, activated HBCs give rise to GBCs that persist for months and continue to act as bona fide stem cells by participating in tissue maintenance and regeneration over the long term. Our analysis provides mechanistic insight into the dynamics between tissue stem cell subtypes and demonstrates that p63 regulates the reserve state but not the stem cell status of HBCs.

scholarly journals Patterns of Cell Division and the Risk of Cancer

Genetics ◽  
2003 ◽  
Vol 163 (4) ◽  
pp. 1527-1532 ◽  
Author(s):  
Steven A Frank ◽  
Yoh Iwasa ◽  
Martin A Nowak
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Basal Layer ◽  
Mutation Rates ◽  
Tissue Architecture ◽  
Cell Lineages ◽  
Cell Mutation ◽  
Long Stem ◽  
Risk Of Cancer ◽  
Transit Cell

Abstract Epidermal and intestinal tissues divide throughout life to replace lost surface cells. These renewing tissues have long-lived basal stem cell lineages that divide many times, each division producing one stem cell and one transit cell. The transit cell divides a limited number of times, producing cells that move up from the basal layer and eventually slough off from the surface. If mutation rates are the same in stem and transit divisions, we show that minimal cancer risk is obtained by using the fewest possible stem divisions subject to the constraints imposed by the need to renew the tissue. In this case, stem cells are a necessary risk imposed by the constraints of tissue architecture. Cairns suggested that stem cells may have lower mutation rates than transit cells do. We develop a mathematical model to study the consequences of different stem and transit mutation rates. Our model shows that stem cell mutation rates two or three orders of magnitude less than transit mutation rates may favor relatively more stem divisions and fewer transit divisions, perhaps explaining how renewing tissues allocate cell divisions between long stem and short transit lineages.

scholarly journals Phase Separation and Mechanical Forces in Regulating Asymmetric Cell Division of Neural Stem Cells

2021 ◽  
Vol 22 (19) ◽  
pp. 10267
Author(s):  
Yiqing Zhang ◽  
Heyang Wei ◽  
Wenyu Wen
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Phase Separation ◽  
Cell Division ◽  
Neural Stem Cells ◽  
Asymmetric Cell Division ◽  
Stem Cell Population ◽  
Mechanical Forces ◽  
Major Mechanism ◽  
Asymmetrically Distributed

Asymmetric cell division (ACD) of neural stem cells and progenitors not only renews the stem cell population but also ensures the normal development of the nervous system, producing various types of neurons with different shapes and functions in the brain. One major mechanism to achieve ACD is the asymmetric localization and uneven segregation of intracellular proteins and organelles into sibling cells. Recent studies have demonstrated that liquid-liquid phase separation (LLPS) provides a potential mechanism for the formation of membrane-less biomolecular condensates that are asymmetrically distributed on limited membrane regions. Moreover, mechanical forces have emerged as pivotal regulators of asymmetric neural stem cell division by generating sibling cell size asymmetry. In this review, we will summarize recent discoveries of ACD mechanisms driven by LLPS and mechanical forces.

scholarly journals 3D Differentiation Of Mammosphere Derived Macaca fascicularis’s Mammary Stem Cells

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Silmi Mariya
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mammary Gland ◽  
Cell Population ◽  
Mammary Stem Cell ◽  
Stem Cell Population ◽  
Stem Cell Markers ◽  
Mammary Stem Cells ◽  
Surgical Biopsy ◽  
Mammary Stem

The mammary gland contains adult stem cells that are capable of self-renewal.  This population plays an important role in the development of mammary gland and breast cancer pathogenesis. The studies of mammary stem cells are limited due to the difficulty to acquire and expand adult stem cell population in an undifferentiated state. In this study, we developed mammosphere cultures of nulliparous cynomolgus monkeys (Macaca fascicularis; Mf) as a culture system to enrich mammary stem cells. This species has similarity of mammary gland structure as humans including anatomy, developmental stages, and lobule profile of mammary gland. The use of stem cells from primate animals is essential to bridge the knowledge gaps resulting from stem cell research using rodents for clinical trials in human. Small samples of mammary tissues were collected by surgical biopsy; cells were cultured as monolayer and cryopreserved. Cryopreserved cells were cultured into mammospheres, and the expression of markers for mammary stem cells was evaluated using qPCR. Cells were further differentiated with 3D approaches to evaluate morphology and organoid budding. The study showed that mammosphere culture resulted in an increase in the expression of mammary stem cell markers with each passage. The 3D differentiation in matrigel allowed for organoid formation. Mammary gland stem cells have been successfully differentiated which characterized by CSN2 marker expression and differentiation regulators marker STAT5 and GATA3. The results indicate that mammospheres can be successfully developed derived from breast tissue of nulliparous Mf collected via surgical biopsy. As the mammosphere allows for enrichment of mammary stem cell population, the findings also suggest that a 3-dimensional system is efficient as in-vitro model to study mammary stem cells and a useful system to study mammary differentiation in regards to cancer prevention.

scholarly journals me31B regulates stem cell homeostasis by preventing excess dedifferentiation in the Drosophila male germline

2021 ◽  
Author(s):  
Lindy Jensen ◽  
Zsolt G. Venkei ◽  
George J. Watase ◽  
Bitarka Bisai ◽  
Scott Pletcher ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Critical Role ◽  
Stem Cell Population ◽  
Germline Stem Cells ◽  
Cell Identity ◽  
Stem Cell Maintenance ◽  
Differentiated Cells ◽  
Male Germline ◽  
Elevated Frequency

Tissue-specific stem cells maintain tissue homeostasis by providing a continuous supply of differentiated cells throughout the life of organisms. Differentiated/differentiating cells can revert back to a stem cell identity via dedifferentiation to help maintain the stem cell pool beyond the lifetime of individual stem cells. Although dedifferentiation is important to maintain the stem cell population, it is speculated to underlie tumorigenesis. Therefore, this process must be tightly controlled. Here we show that a translational regulator me31B plays a critical role in preventing excess dedifferentiation in the Drosophila male germline: in the absence of me31B, spermatogonia (SGs) dedifferentiate into germline stem cells (GSCs) at a dramatically elevated frequency. Our results show that the excess dedifferentiation is likely due to misregulation of nos, a key regulator of germ cell identity and GSC maintenance. Taken together, our data reveal negative regulation of dedifferentiation to balance stem cell maintenance with differentiation.

scholarly journals Cellular and molecular characterization of the role of the flk-2/flt-3 receptor tyrosine kinase in hematopoietic stem cells

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2422-2430 ◽  
Author(s):  
FC Zeigler ◽  
BD Bennett ◽  
CT Jordan ◽  
SD Spencer ◽  
S Baumhueter ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tyrosine Kinase ◽  
Hematopoietic Stem Cell ◽  
Receptor Tyrosine Kinase ◽  
Lymphoid Cells ◽  
Stem Cell Population ◽  
Cell Populations ◽  
Hematopoietic Stem ◽  
Stem Cell Populations

The flk-2/flt-3 receptor tyrosine kinase was cloned from a hematopoietic stem cell population and is considered to play a potential role in the developmental fate of the stem cell. Using antibodies derived against the extracellular domain of the receptor, we show that stem cells from both murine fetal liver and bone marrow can express flk-2/flt-3. However, in both these tissues, there are stem cell populations that do not express the receptor. Cell cycle analysis shows that stem cells that do not express the receptor have a greater percentage of the population in G0 when compared with the flk-2/flt-3- positive population. Development of agonist antibodies to the receptor shows a proliferative role for the receptor in stem cell populations. Stimulation with an agonist antibody gives rise to an expansion of both myeloid and lymphoid cells and this effect is enhanced by the addition of kit ligand. These studies serve to further illustrate the importance of the flk-2/flt-3 receptor in the regulation of the hematopoietic stem cell.

scholarly journals Silencing of long noncoding RNA HOXA11-AS inhibits the Wnt signaling pathway via the upregulation of HOXA11 and thereby inhibits the proliferation, invasion, and self-renewal of hepatocellular carcinoma stem cells

2019 ◽  
Vol 51 (11) ◽  
pp. 1-20 ◽  
Author(s):  
Jun-Cheng Guo ◽  
Yi-Jun Yang ◽  
Jin-Fang Zheng ◽  
Jian-Quan Zhang ◽  
Min Guo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Stem Cell ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Methylation Level ◽  
Wnt Signaling Pathway ◽  
The Self ◽  
Self Renewal

AbstractHepatocellular carcinoma (HCC) is a major cause of cancer-related deaths, but its molecular mechanisms are not yet well characterized. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis, including that of HCC. However, the role of homeobox A11 antisense (HOXA11-AS) in determining HCC stem cell characteristics remains to be explained; hence, this study aimed to investigate the effects of HOXA11-AS on HCC stem cell characteristics. Initially, the expression patterns of HOXA11-AS and HOXA11 in HCC tissues, cells, and stem cells were determined. HCC stem cells, successfully sorted from Hep3B and Huh7 cells, were transfected with short hairpin or overexpression plasmids for HOXA11-AS or HOXA11 overexpression and depletion, with an aim to study the influences of these mediators on the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo. Additionally, the potential relationship and the regulatory mechanisms that link HOXA11-AS, HOXA11, and the Wnt signaling pathway were explored through treatment with Dickkopf-1 (a Wnt signaling pathway inhibitor). HCC stem cells showed high expression of HOXA11-AS and low expression of HOXA11. Both HOXA11-AS silencing and HOXA11 overexpression suppressed the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo, as evidenced by the decreased expression of cancer stem cell surface markers (CD133 and CD44) and stemness-related transcription factors (Nanog, Sox2, and Oct4). Moreover, silencing HOXA11-AS inactivated the Wnt signaling pathway by decreasing the methylation level of the HOXA11 promoter, thereby inhibiting HCC stem cell characteristics. Collectively, this study suggested that HOXA11-AS silencing exerts an antitumor effect, suppressing HCC development via Wnt signaling pathway inactivation by decreasing the methylation level of the HOXA11 promoter.

scholarly journals The Epidermal Stem Cell Compartment: Variation in Expression Levels of E–Cadherin and Catenins Within the Basal Layer of Human Epidermis

1997 ◽  
Vol 45 (6) ◽  
pp. 867-874 ◽  
Author(s):  
Jean-Pierre Molès ◽  
Fiona M. Watt
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Basal Layer ◽  
Human Epidermis ◽  
Proliferative Potential ◽  
Stem Cell Markers ◽  
Cell Compartment ◽  
Stem Cell Compartment ◽  
E Cadherin ◽  
Cell Cell

The basal layer of the epidermis contains two types of proliferating keratinocyte: stem cells, with high proliferative potential, and transit amplifying cells, which are destined to undergo terminal differentiation after a few rounds of division. It has been shown previously that two- to three-fold differences in the average staining intensity of fluorescein-conjugated antibodies to β1 integrin subunits reflect profound differences in the proliferative potential of keratinocytes, with integrin-bright populations being enriched for stem cells. In the search for additional stem cell markers, we have stained sections of normal human epidermis with antibodies to proteins involved in intercellular adhesion and quantitated the fluorescence of individual cell-cell borders. In the basal layer, patches of brightly labeled cells were detected with antibodies to E-cadherin, β-catenin, and γ-catenin, but not with antibodies to P-cadherin, α-catenin, or with pan-desmocollin and pan-desmoglein antibodies. In the body sites examined, palm and foreskin, integrinbright regions were strongly labeled for γ-catenin and weakly labeled for E-cadherin and β-catenin. Our data suggest that there are gradients of both cell-cell and cell-extracellular matrix adhesiveness within the epidermal basal layer and that the levels of E-cadherin and of β-and γ-catenin may provide markers for the stem cell compartment, stem cells expressing relatively higher levels of γ-catenin and lower levels of E-cadherin and β-catenin than other basal keratinocytes.

scholarly journals 5-Azacytidine-Induced Cardiomyocyte Differentiation of Very Small Embryonic-Like Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
XiaoLin Sun ◽  
HongXiao Li ◽  
Ye Zhu ◽  
Pei Xu ◽  
QiSheng Zuo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Ethical Issues ◽  
Troponin T ◽  
Embryonic Stem ◽  
Stem Cell Population ◽  
Pacemaker Activity ◽  
Stem Cell Markers ◽  
Seed Cells

The use of stem cells in generating cell-based pacemaker therapies for bradyarrhythmia is currently being considered. Due to the propensity of stem cells to form tumors, as well as ethical issues surrounding their use, the seed cells used in cardiac biological pacemakers have limitations. Very small embryonic-like stem cells (VSELs) are a unique and rare adult stem cell population, which have the same structural, genetic, biochemical, and functional characteristics as embryonic stem cells without the ethical controversy. In this study, we investigated the ability of rat bone marrow- (BM-) derived VSELs to differentiate in vitro into cardiomyocytes by 5-Azacytidine (5-AzaC) treatment. The morphology of VSELs treated with 10 μM 5-AzaC increased in volume and gradually changed to cardiomyocyte-like morphology without massive cell death. Additionally, mRNA expression of the cardiomyocyte markers cardiac troponin-T (cTnT) and α-sarcomeric actin (α-actin) was significantly upregulated after 5-AzaC treatment. Conversely, stem cell markers such as Nanog, Oct-4, and Sox2 were continuously downregulated posttreatment. On day 14 post-5-AzaC treatment, the positive expression rates of cTnT and α-actin were 18.41±1.51% and 19.43±0.51%, respectively. Taken together, our results showed that rat BM-VSELs have the ability to differentiate into cardiomyocytes in vitro. These findings suggest that VSELs would be useful as seed cells in exploring the mechanism of biological pacemaker activity.

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