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.

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 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 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 Integrins control the positioning and proliferation of follicle stem cells in the Drosophila ovary

2008 ◽  
Vol 182 (4) ◽  
pp. 801-815 ◽  
Author(s):  
Alana M. O'Reilly ◽  
Hsiu-Hsiang Lee ◽  
Michael A. Simon
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Cell Communication ◽  
Self Renewal ◽  
Ovarian Stem Cells ◽  
Stem Cell Populations ◽  
Integrin Ligand ◽  
Follicle Stem Cells ◽  
Drosophila Ovary

Adult stem cells are maintained in specialized microenvironments called niches, which promote self-renewal and prevent differentiation. In this study, we show that follicle stem cells (FSCs) in the Drosophila melanogaster ovary rely on cues that are distinct from those of other ovarian stem cells to establish and maintain their unique niche. We demonstrate that integrins anchor FSCs to the basal lamina, enabling FSCs to maintain their characteristic morphology and position. Integrin-mediated FSC anchoring is also essential for proper development of differentiating prefollicle cells that arise from asymmetrical FSC divisions. Our results support a model in which FSCs contribute to the formation and maintenance of their own niche by producing the integrin ligand, laminin A (LanA). Together, LanA and integrins control FSC proliferation rates, a role that is separable from their function in FSC anchoring. Importantly, LanA-integrin function is not required to maintain other ovarian stem cell populations, demonstrating that distinct pathways regulate niche–stem cell communication within the same organ.

scholarly journals Identification of Distinct Breast Cancer Stem Cell Populations Based on Single-Cell Analyses of Functionally Enriched Stem and Progenitor Pools

2016 ◽  
Vol 6 (1) ◽  
pp. 121-136 ◽  
Author(s):  
Nina Akrap ◽  
Daniel Andersson ◽  
Eva Bom ◽  
Pernilla Gregersson ◽  
Anders Ståhlberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Single Cell ◽  
Breast Cancer Stem Cell ◽  
Cell Populations ◽  
Stem Cell Populations

scholarly journals Transcriptional and Functional Description of Stem Cell Heterogeneity in Native and Transplantation Hematopoiesis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3844-3844
Author(s):  
Alejo E Rodriguez-Fraticelli ◽  
Caleb Weinreb ◽  
Allon Moshe Klein ◽  
Fernando Camargo
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Steady State ◽  
Hematopoietic Stem Cells ◽  
Single Cell ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Significant Proportion ◽  
Cell Heterogeneity ◽  
Hematopoietic Stem

Abstract The hematopoietic system follows a hierarchical organization, with multipotent long-term repopulating hematopoietic stem cells (LT-HSCs) occupying the top tier. This paradigm, developed mostly through cell transplantation assays, has recently been contested by a series of studies performed under native conditions, without transplantation. Application of systems-level single cell methods in this setting has revealed a heterogeneity of cell states within progenitors and stem cells, prompting a reevaluation of the theories of hematopoietic lineage fate decisions. We have previously described that hematopoietic stem cell fates are clonally heterogeneous under steady state and uncovered that a fraction of LT-HSCs contributes to a significant proportion of the megakaryocytic cell lineage under steady state, while rarely generating other types of progeny in unperturbed conditions. To elucidate the molecular underpinnings of this functional lineage-output heterogeneity, we developed a technique to barcode hematopoietic cells at the RNA level in order to simultaneously capture the lineage relationships and transcriptional states of HSCs. Using a droplet-based massive single cell RNAseq platform, we analyzed thousands of engrafted hematopoietic stem cells together with a sufficiently significant representation of downstream progenitor cells to measure HSC output. Inspection of the resulting "stem cell state-fate maps" revealed a variety of stem cell behaviors, including single cell quiescence, asymmetric and symmetric divisions, and clonal expansion. We also connected these behaviors with some of the previously observed heterogeneity in stem cell outcomes, including lineage bias, lineage output and clonal competition. Importantly, clustering of expression profiles revealed significant differences in the transcriptional programs related with some of these behaviors, which illuminate the molecular machineries that operate at the stem cell level to define this heterogeneity. Thus, our work has identified potential novel mediators for stem cell heterogeneity, which we are functionally analyzing in further detail to understand their molecular mechanisms. Disclosures No relevant conflicts of interest to declare.

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.

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