Stem Cell Niche Dynamics: From Homeostasis to Carcinogenesis

The stem cell microenvironment is involved in regulating the fate of the stem cell with respect to self-renewal, quiescence, and differentiation. Mathematical models are helpful in understanding how key pathways regulate the dynamics of stem cell maintenance and homeostasis. This tight regulation and maintenance of stem cell number is thought to break down during carcinogenesis. As a result, the stem cell niche has become a novel target of cancer therapeutics. Developing a quantitative understanding of the regulatory pathways that guide stem cell behavior will be vital to understanding how these systems change under conditions of stress, inflammation, and cancer initiation. Predictions from mathematical modeling can be used as a clinical tool to guide therapy design. We present a survey of mathematical models used to study stem cell population dynamics and stem cell niche regulation, both in the hematopoietic system and other tissues. Highlighting the quantitative aspects of stem cell biology, we describe compelling questions that can be addressed with modeling. Finally, we discuss experimental systems, most notably Drosophila, that can best be used to validate mathematical predictions.

• Publication year

  2012

• Venue

  Stem Cells International

• Publication date

  2012-02-09

• Fields of study

  Biology, Mathematics, Medicine

• Identifiers
  DOI 10.1155/2012/367567PMID 22448171PMCID 3289927
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Predictions from mathematical modeling can serve as a clinical tool to guide cancer therapy design targeting the stem cell niche.

  Confidence 0.85

  Killer Whale (322360f1c1) extractionq (76h6bfydm6) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• Drosophila is identified as the experimental system best suited for validating mathematical predictions about stem cell niche behavior.

  Confidence 0.88

  Killer Whale (322360f1c1) extractionq (76h6bfydm6) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review

• cancer therapeutics

  therapeutic approach

  Treatment approaches for which the stem cell niche has become a novel target, with mathematical modeling proposed as a design guide.

  Aliases: cancer therapy

  Killer Whale (322360f1c1) extractionq (76h6bfydm6) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• carcinogenesis

  biological process, disease process

  The process of cancer initiation in which tight regulation of stem cell number is thought to break down.

  Aliases: cancer initiation

  Killer Whale (322360f1c1) extractionq (76h6bfydm6) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• drosophila

  model organism

  A model organism highlighted as particularly well-suited for experimentally validating mathematical predictions about stem cell niche dynamics.

  Killer Whale (322360f1c1) extractionq (76h6bfydm6) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• hematopoietic system

  biological system

  The blood-forming tissue system used as a primary context for reviewing mathematical models of stem cell regulation.

  Aliases: hematopoietic stem cell niche

  Killer Whale (322360f1c1) extractionq (76h6bfydm6) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• homeostasis

  biological process

  The tightly regulated maintenance of stem cell numbers in normal tissue, which breaks down during carcinogenesis.

  Aliases: stem cell homeostasis

  Killer Whale (322360f1c1) extractionq (76h6bfydm6) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• mathematical modeling

  method

  Quantitative frameworks used in this paper to study stem cell population dynamics and niche regulatory pathways.

  Aliases: mathematical models

  Killer Whale (322360f1c1) extractionq (76h6bfydm6) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• stem cell niche

  biological structure, regulatory system

  The microenvironment surrounding stem cells that regulates their fate decisions including self-renewal, quiescence, and differentiation.

  Aliases: stem cell microenvironment

  Killer Whale (322360f1c1) extractionq (76h6bfydm6) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• stem cell population dynamics

  biological process

  The quantitative changes in stem cell numbers over time governed by self-renewal, differentiation, and quiescence.

  Killer Whale (322360f1c1) extractionq (76h6bfydm6) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review

• Cancer stem cells in solid tumors: is 'evading apoptosis' a hallmark of cancer?

  2011cited by this paper
• Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state

  2011cited by this paper
• Regulation of Cancer Stem Cells by Cytokine Networks: Attacking Cancer's Inflammatory Roots

  2011cited by this paper
• Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells.

  2011cited by this paper
• Leukemia stem cells and microenvironment: biology and therapeutic targeting.

  2011cited by this paper
• Organism-scale modeling of early Drosophila patterning via bone morphogenetic proteins.

  2010cited by this paper
• The diffusive finite state projection algorithm for efficient simulation of the stochastic reaction-diffusion master equation.

  2010cited by this paper
• Transformed epithelial cells and fibroblasts/myofibroblasts interaction in breast tumor: a mathematical model and experiments

  2010cited by this paper
• Inhibition of Notch Signaling in Glioblastoma Targets Cancer Stem Cells via an Endothelial Cell Intermediate

  2010cited by this paper
• Mathematical modelling and experiments for the proliferation and differentiation of Drosophila intestinal stem cells I

  2010cited by this paper
• JAK–STAT is restrained by Notch to control cell proliferation of the Drosophila intestinal stem cells

  2010cited by this paper
• Dual function of MyD88 in RAS signaling and inflammation, leading to mouse and human cell transformation.

  2010cited by this paper
• Stem cells in human breast cancer.

  2010cited by this paper
• Cancer stem cells: nature versus nurture

  2010cited by this paper
• Identification of cancer stem cells in Ewing's sarcoma.

  2009cited by this paper
• Breast cancer stem cells and intrinsic subtypes: controversies rage on.

  2009cited by this paper
• Mechanisms of stem cell self-renewal.

  2009influential reference
• Paradoxical dependencies of tumor dormancy and progression on basic cell kinetics.

  2009cited by this paper
• Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut.

  2009cited by this paper
• Differential destruction of stem cells: implications for targeted cancer stem cell therapy.

  2009cited by this paper
• The leukemic stem cell niche: current concepts and therapeutic opportunities.

  2009cited by this paper
• The tumor suppressor p53 regulates polarity of self-renewing divisions in mammary stem cells.

  2009cited by this paper
• Adenomatous polyposis coli regulates Drosophila intestinal stem cell proliferation

  2009cited by this paper
• Identification of cells initiating human melanomas

  2008cited by this paper
• Simulation of proliferation and differentiation of cells in a stem-cell niche

  2008cited by this paper
• Physical modeling of cell geometric order in an epithelial tissue

  2008cited by this paper
• Stem cell regulation and the development of blast crisis in chronic myeloid leukemia: Implications for the outcome of Imatinib treatment and discontinuation.

  2008cited by this paper
• Mathematical models of cancer stem cells.

  2008cited by this paper
• Activation of Wnt Signaling in Hematopoietic Regeneration

  2008cited by this paper
• Drosophila asymmetric division, polarity and cancer

  2008cited by this paper
• HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion

  2008cited by this paper
• How dysregulated colonic crypt dynamics cause stem cell overpopulation and initiate colon cancer.

  2008cited by this paper
• Cancer stem cells in solid tumors.

  2007cited by this paper
• A human colon cancer cell capable of initiating tumour growth in immunodeficient mice

  2007cited by this paper
• Regulation of spindle orientation and neural stem cell fate in the Drosophila optic lobe

  2007cited by this paper
• Hematopoietic stem-cell behavior in nonhuman primates.

  2007cited by this paper
• Multipotent Drosophila Intestinal Stem Cells Specify Daughter Cell Fates by Differential Notch Signaling

  2007cited by this paper
• Mammary Stem Cells and Breast Cancer—Role of Notch Signalling

  2007cited by this paper
• Notch signaling, gamma-secretase inhibitors, and cancer therapy.

  2007cited by this paper
• Stochastic modeling of cellular colonies with quiescence: an application to drug resistance in cancer.

  2007cited by this paper
• Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma

  2007cited by this paper
• Symmetric Division of Cancer Stem Cells – a Key Mechanism in Tumor Growth that should be Targeted in Future Therapeutic Approaches

  2007cited by this paper
• Symmetric division of cancer stem cells--a key mechanism in tumor growth that should be targeted in future therapeutic approaches.

  2007cited by this paper
• The hematopoietic stem cell and its niche: a comparative view.

  2007cited by this paper
• Successful Therapy Must Eradicate Cancer Stem Cells

  2006cited by this paper
• The adult Drosophila posterior midgut is maintained by pluripotent stem cells

  2006cited by this paper
• Asymmetric and symmetric stem-cell divisions in development and cancer

  2006influential reference
• Quantitative models of developmental pattern formation.

  2006cited by this paper
• Stochastic Modelling for Systems Biology

  2006cited by this paper
• The unpredictable stem cell

  2006cited by this paper
• Stem Cells and Their Niches

  2006cited by this paper
• Asymmetry of stem cell fate and the potential impact of the niche

  2006cited by this paper
• Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster

  2005cited by this paper
• Signaling in stem cell niches: lessons from the Drosophila germline

  2005cited by this paper
• Urological Survey UROLOGICAL ONCOLOGY: PROSTATE CANCER Hedgehog Signalling in Prostate Regeneration, Neoplasia and Metastasis

  2005cited by this paper
• Dynamics of chronic myeloid leukaemia

  2005cited by this paper
• The nature of stem cells: state rather than entity

  2004cited by this paper
• Hedgehog-interacting protein is highly expressed in endothelial cells but down-regulated during angiogenesis and in several human tumors

  2004cited by this paper
• Characterization of clonogenic multiple myeloma cells.

  2004cited by this paper
• Diverse mechanisms regulate stem cell self-renewal.

  2004cited by this paper
• Dynamics of cancer progression

  2004cited by this paper
• Identification of human brain tumour initiating cells

  2004cited by this paper
• The stem cell niche: theme and variations.

  2004cited by this paper
• Regulation of human breast epithelial stem cells

  2003cited by this paper
• Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells

  2003cited by this paper
• Prospective identification of tumorigenic breast cancer cells

  2003cited by this paper
• Mouse models of human breast cancer: evolution or convolution?

  2003cited by this paper
• Stem cells in normal breast development and breast cancer

  2003cited by this paper
• Applying the principles of stem-cell biology to cancer

  2003cited by this paper
• Intestinal stem cells protect their genome by selective segregation of template DNA strands.

  2002cited by this paper
• Evidence that the number of hematopoietic stem cells per animal is conserved in mammals.

  2002cited by this paper
• In vivo kinetics of murine hemopoietic stem cells.

  2000cited by this paper
• Evidence that hematopoiesis may be a stochastic process in vivo

  1996cited by this paper
• Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study.

  1995cited by this paper
• Biologically motivated two-stage model for cancer risk assessment.

  1988cited by this paper
• Model for the incidence of embryonal cancers: application to retinoblastoma.

  1978cited by this paper
• The Genetics and Biology of Drosophila

  1976cited by this paper
• Positional information and the spatial pattern of cellular differentiation.

  1969cited by this paper
• Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences is currently published by The Royal

  1951cited by this paper

• Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis

  2025cites this paper
• FlyRNAi.org 2025 update—expanded resources for new technologies and species

  2024cites this paper
• Novel Strategy in Searching for Natural Compounds with Anti-Aging and Rejuvenating Potential

  2023cites this paper
• Mathematical Modeling Reveals the Role of Hypoxia in the Promotion of Human Mesenchymal Stem Cell Long-Term Expansion

  2018cites this paper
• Physiology of Stem Cells

  2017cites this paper
• Towards Quantitative Systems Pharmacology Models of Chemotherapy‐Induced Neutropenia

  2017cites this paper
• Near Equilibrium Calculus of Stem Cells in Application to the Airway Epithelium Lineage

  2016cites this paper
• Effects of surgery on the cancer stem cell niche.

  2016cites this paper
• Evaluating tactile feedback in robotic surgery for potential clinical application using an animal model

  2016cites this paper
• Structured Models and Their Use in Modeling Anticancer Therapies

  2016cites this paper
• The impact of tumor stroma on drug response in breast cancer.

  2015cites this paper
• cD 44 + / cD 24-breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide RADA 16 nanofiber scaffold

  2015cites this paper
• CD44+/CD24− breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide RADA16 nanofiber scaffold

  2015cites this paper
• A quantitative analysis of stem cell homeostasis in the Arabidopsis columella root cap

  2015cites this paper
• Stochasticity and determinism in models of hematopoiesis.

  2014cites this paper
• Computational Modeling and Stem Cell Engineering

  2014cites this paper
• A Systems Biology Approach to Blood

  2014influential citation
• Structured population models of cell differentiation

  2014cites this paper
• Alteration of radiation-sensitive processes associated with cancer and longevity by dietary 2-mercaptoethanol.

  2014cites this paper
• The Stem Cell Niche as the Key to Early Cancer Development

  2013cites this paper
• EZH2 T416 Phosphorylation Enhances Breast Cancer Tumorigenesis

  2013cites this paper