scholarly journals The nutritional environment determines which and how intestinal stem cells contribute to homeostasis and tumorigenesis

2019 ◽  
Vol 40 (8) ◽  
pp. 937-946 ◽  
Author(s):  
Wenge Li ◽  
Samuel E Zimmerman ◽  
Karina Peregrina ◽  
Michele Houston ◽  
Joshua Mayoral ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tumor Development ◽  
Intestinal Cell ◽  
Cell Populations ◽  
Dna Mismatch ◽  
Nutrient Environment ◽  
Mucosal Homeostasis ◽  
Human Mucosa ◽  
Stem Cell Populations

Abstract Sporadic colon cancer accounts for approximately 80% of colorectal cancer (CRC) with high incidence in Western societies strongly linked to long-term dietary patterns. A unique mouse model for sporadic CRC results from feeding a purified rodent Western-style diet (NWD1) recapitulating intake for the mouse of common nutrient risk factors each at its level consumed in higher risk Western populations. This causes sporadic large and small intestinal tumors in wild-type mice at an incidence and frequency similar to that in humans. NWD1 perturbs intestinal cell maturation and Wnt signaling throughout villi and colonic crypts and decreases mouse Lgr5hi intestinal stem cell contribution to homeostasis and tumor development. Here we establish that NWD1 transcriptionally reprograms Lgr5hi cells, and that nutrients are interactive in reprogramming. Furthermore, the DNA mismatch repair pathway is elevated in Lgr5hi cells by lower vitamin D3 and/or calcium in NWD1, paralleled by reduced accumulation of relevant somatic mutations detected by single-cell exome sequencing. In compensation, NWD1 also reprograms Bmi1+ cells to function and persist as stem-like cells in mucosal homeostasis and tumor development. The data establish the key role of the nutrient environment in defining the contribution of two different stem cell populations to both mucosal homeostasis and tumorigenesis. This raises important questions regarding impact of variable human diets on which and how stem cell populations function in the human mucosa and give rise to tumors. Moreover, major differences reported in turnover of human and mouse crypt base stem cells may be linked to their very different nutrient exposures.

scholarly journals Quiescent, Slow-Cycling Stem Cell Populations in Cancer: A Review of the Evidence and Discussion of Significance

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Nathan Moore ◽  
Stephen Lyle
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Adult Stem Cells ◽  
Cell Populations ◽  
Proliferative Potential ◽  
Cell Cycle Regulators ◽  
Slow Cycling ◽  
Stem Cell Populations

Long-lived cancer stem cells (CSCs) with indefinite proliferative potential have been identified in multiple epithelial cancer types. These cells are likely derived from transformed adult stem cells and are thought to share many characteristics with their parental population, including a quiescent slow-cycling phenotype. Various label-retaining techniques have been used to identify normal slow cycling adult stem cell populations and offer a unique methodology to functionally identify and isolate cancer stem cells. The quiescent nature of CSCs represents an inherent mechanism that at least partially explains chemotherapy resistance and recurrence in posttherapy cancer patients. Isolating and understanding the cell cycle regulatory mechanisms of quiescent cancer cells will be a key component to creation of future therapies that better target CSCs and totally eradicate tumors. Here we review the evidence for quiescent CSC populations and explore potential cell cycle regulators that may serve as future targets for elimination of these cells.

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.

Leukemic stem cells hiding in plain sight

2019 ◽  
Vol 4 (38) ◽  
pp. eaay7253
Author(s):  
Gabriel K. Griffin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Immune Surveillance ◽  
Cell Populations ◽  
Leukemic Stem Cell ◽  
Leukemic Stem Cells ◽  
Stem Cell Populations

Activation of NK-mediated immune surveillance clears leukemic stem cell populations.

scholarly journals Comparative proteomic analysis of two distinct stem-cell populations from human amniotic fluid

2015 ◽  
Vol 11 (6) ◽  
pp. 1622-1632 ◽  
Author(s):  
Rita Romani ◽  
Francesca Fallarino ◽  
Irene Pirisinu ◽  
Mario Calvitti ◽  
Anna Caselli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Amniotic Fluid ◽  
Proteomic Analysis ◽  
Cell Populations ◽  
Human Amniotic Fluid ◽  
Comparative Proteomic Analysis ◽  
Stem Cell Populations

Characterization of two types of stem cells isolated from human amniotic fluid.

scholarly journals Stem cells: Aging and transcriptional fingerprints

2017 ◽  
Vol 217 (1) ◽  
pp. 79-92 ◽  
Author(s):  
Brice E. Keyes ◽  
Elaine Fuchs
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Function ◽  
Cell Types ◽  
Cell Populations ◽  
Functional Abilities ◽  
Future Directions ◽  
Age Related ◽  
Transcriptional Changes ◽  
Stem Cell Populations

Stem cells are imbued with unique qualities. They have the capacity to propagate themselves through symmetric divisions and to divide asymmetrically to engender new cells that can progress to differentiate into tissue-specific, terminal cell types. Armed with these qualities, stem cells in adult tissues are tasked with replacing decaying cells and regenerating tissue after injury to maintain optimal tissue function. With increasing age, stem cell functional abilities decline, resulting in reduced organ function and delays in tissue repair. Here, we review the effect of aging in five well-studied adult murine stem cell populations and explore age-related declines in stem cell function and their consequences for stem cell self-renewal, tissue homeostasis, and regeneration. Finally, we examine transcriptional changes that have been documented in aged stem cell populations and discuss new questions and future directions that this collection of data has uncovered.

scholarly journals Cardiac Stem Cells in the Postnatal Heart: Lessons from Development

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Cristina Aguilar-Sanchez ◽  
Melina Michael ◽  
Sari Pennings
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Heart Development ◽  
Cell Populations ◽  
Cell Renewal ◽  
Cardiac Stem Cell ◽  
Stem Cell Populations

Heart development in mammals is followed by a postnatal decline in cell proliferation and cell renewal from stem cell populations. A better understanding of the developmental changes in cardiac microenvironments occurring during heart maturation will be informative regarding the loss of adult regenerative potential. We reevaluate the adult heart’s mitotic potential and the reported adult cardiac stem cell populations, as these are two topics of ongoing debate. The heart’s early capacity for cell proliferation driven by progenitors and reciprocal signalling is demonstrated throughout development. The mature heart architecture and environment may be more restrictive on niches that can host progenitor cells. The engraftment issues observed in cardiac stem cell therapy trials using exogenous stem cells may indicate a lack of supporting stem cell niches, while tissue injury adds to a hostile microenvironment for transplanted cells. Engraftment may be improved by preconditioning the cultured stem cells and modulating the microenvironment to host these cells. These prospective areas of further research would benefit from a better understanding of cardiac progenitor interactions with their microenvironment throughout development and may lead to enhanced cardiac niche support for stem cell therapy engraftment.

scholarly journals Endodermal stem cell populations derived from pluripotent stem cells

2013 ◽  
Vol 25 (2) ◽  
pp. 265-271 ◽  
Author(s):  
Xin Cheng ◽  
Amita Tiyaboonchai ◽  
Paul Gadue
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Cell Populations ◽  
Stem Cell Populations

scholarly journals The Middle Part of the Plucked Hair Follicle Outer Root Sheath Is Identified as an Area Rich in Lineage-Specific Stem Cell Markers

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 154
Author(s):  
Hanluo Li ◽  
Federica Francesca Masieri ◽  
Marie Schneider ◽  
Alexander Bartella ◽  
Sebastian Gaus ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Cell Populations ◽  
Stem Cell Markers ◽  
Outer Root Sheath ◽  
Root Sheath ◽  
Gene And Protein Expression ◽  
Stem Cell Populations

Hair follicle outer root sheath (ORS) is a putative source of stem cells with therapeutic capacity. ORS contains several multipotent stem cell populations, primarily in the distal compartment of the bulge region. However, the bulge is routinely obtained using invasive isolation methods, which require human scalp tissue ex vivo. Non-invasive sampling has been standardized by means of the plucking procedure, enabling to reproducibly obtain the mid-ORS part. The mid-ORS shows potential for giving rise to multiple stem cell populations in vitro. To demonstrate the phenotypic features of distal, middle, and proximal ORS parts, gene and protein expression profiles were studied in physically separated portions. The mid-part of the ORS showed a comparable or higher NGFR, nestin/NES, CD34, CD73, CD44, CD133, CK5, PAX3, MITF, and PMEL expression on both protein and gene levels, when compared to the distal ORS part. Distinct subpopulations of cells exhibiting small and round morphology were characterized with flow cytometry as simultaneously expressing CD73/CD271, CD49f/CD105, nestin, and not CK10. Potentially, these distinct subpopulations can give rise to cultured neuroectodermal and mesenchymal stem cell populations in vitro. In conclusion, the mid part of the ORS holds the potential for yielding multiple stem cells, in particular mesenchymal stem cells.

scholarly journals Single cell transcriptomics of human epidermis reveals basal stem cell transition states

2019 ◽  
Author(s):  
Shuxiong Wang ◽  
Michael L. Drummond ◽  
Christian F. Guerrero-Juarez ◽  
Eric Tarapore ◽  
Adam L. MacLean ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Single Cell ◽  
Cell Communication ◽  
Cell Populations ◽  
Cell Heterogeneity ◽  
Stable States ◽  
Interfollicular Epidermis ◽  
Epidermal Homeostasis ◽  
Stem Cell Populations

ABSTRACTHow stem cells give rise to human interfollicular epidermis is unclear despite the crucial role the epidermis plays in barrier and appendage formation. Here we use single cell-RNA sequencing to interrogate basal stem cell heterogeneity of human interfollicular epidermis and find at least four spatially distinct stem cell populations that decorate the top and bottom of rete ridge architecture and hold transitional positions between the basal and suprabasal epidermal layers. Cell-cell communication modeling through co-variance of cognate ligand-receptor pairs indicate that the basal cell populations distinctly serve as critical signaling hubs that maintain epidermal communication. Combining pseudotime, RNA velocity, and cellular entropy analyses point to a hierarchical differentiation lineage supporting multi-stem cell interfollicular epidermal homeostasis models and suggest the “transitional” basal stem cells are stable states essential for proper stratification. Finally, alterations in differentially expressed “transitional” basal stem cell genes result in severe thinning of human skin equivalents, validating their essential role in epidermal homeostasis and reinforcing the critical nature of basal stem cell heterogeneity.

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