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Updated: Aug 14, 2026
Patterning the Geometry of Human Embryonic Stem Cell Colonies on Compliant Substrates to Control Tissue-Level Mechanics
Published on: September 28, 2019
A three-dimensional model to study the epigenetic effects induced by the microenvironment of human embryonic stem
Lynne-Marie Postovit1, Elisabeth A Seftor, Richard E B Seftor
1Children's Memorial Research Center, Chicago, Illinois 60614, USA.
Abstract:
New methods of study are necessary to define the homeostatic mechanisms that regulate stem cell properties and to determine the possible epigenetic influence of the stem cell microenvironment on the phenotype of tumor cells. We recently demonstrated that the tumorgenicity of aggressive cutaneous melanoma cells can be abrogated by the zebrafish embryonic microenvironment. We have developed a three-dimensional (3D) model, as a corollary of these findings, that allows melanoma cells to be exposed to the microenvironment of human embryonic stem cells (hESCs). Using this methodology, we determined that hESC microenvironments can dramatically influence the behavior of aggressive melanoma cells. Specifically, exposure of tumor cells to H1- or HSF-6-hESC matrices induced a melanocyte-like phenotype with the ability to form colonies similar to hESCs. Furthermore, melanoma cells were less invasive after culture on hESC microenvironments. These findings demonstrate the utility of this 3D model for studying the unique factors deposited by hESCs and for investigating the epigenetic effects that stem cell microenvironments may have on tumor progression.
Insights
Human embryonic stem cell (hESC) microenvironments can reprogram aggressive melanoma cells. A novel 3D model shows tumor cells gain a melanocyte-like phenotype and reduce invasiveness when exposed to hESC matrices.
Area of Science:
- Stem cell biology
- Cancer research
- Epigenetics
Background:
- Understanding stem cell homeostasis and microenvironmental influences on tumor cells is crucial.
- Previous work showed zebrafish microenvironments can reduce melanoma tumorgenicity.
- A need exists for models to study stem cell microenvironment effects on cancer progression.
Purpose of the Study:
- To develop and utilize a 3D model to investigate the impact of human embryonic stem cell (hESC) microenvironments on aggressive melanoma cells.
- To determine if hESC microenvironments can alter the phenotype and behavior of tumor cells.
- To explore the potential epigenetic reprogramming of cancer cells by stem cell niches.
Main Methods:
- Development of a three-dimensional (3D) culture model exposing melanoma cells to hESC microenvironments.
- Utilizing H1- and HSF-6-hESC matrices for co-culture experiments.
- Assessing changes in melanoma cell phenotype, colony formation, and invasiveness.
Main Results:
- Melanoma cells cultured in hESC microenvironments exhibited a melanocyte-like phenotype.
- Tumor cells demonstrated an ability to form colonies comparable to hESCs.
- Melanoma cell invasiveness was significantly reduced after exposure to hESC matrices.
Conclusions:
- hESC microenvironments can profoundly influence the behavior and phenotype of aggressive melanoma cells.
- The developed 3D model is effective for studying stem cell-derived factors and their epigenetic effects on tumor progression.
- This research highlights the potential of stem cell niches in modulating cancer characteristics.
