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The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
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The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
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A hair follicle or HF is a small part of the skin that produces the hair shaft. Paul Gerson Unna was the first to observe a bulge in the human hair follicle's outer root sheath (ORS). The bulge is present between the sebaceous gland and the arrector pili muscle and is the niche for hair follicle stem cells (HFSCs). The bulge is also a niche for melanocyte stem cells, and their loss results in graying of hair. The HFSCs express Sox9 and Lhx2, which help them maintain stemness and prevent...
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The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
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Stem cell research aims to find ways to use stem cells to regenerate and repair cellular damage. Over time, most adult cells undergo the wear and tear of aging and lose their ability to divide and repair themselves. Stem cells do not display a particular morphology or function. Adult stem cells, which exist as a small subset of cells in most tissues, keep dividing and can differentiate into a number of specialized cells generally formed by that tissue. These cells enable the body to renew and...
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Stochasticity and Spatial Interaction Govern Stem Cell Differentiation Dynamics.

Quinton Smith1, Evgeny Stukalin2, Sravanti Kusuma3

  • 1Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218.

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Stem cells adjust their differentiation based on neighboring cells, influencing tissue growth and disease. Cell-cell interactions and randomness are key drivers of stem cell fate in mixed populations.

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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Quantitative Biology

Background:

  • Stem cell differentiation is crucial for development, tissue repair, and disease.
  • Understanding cell-cell interactions is vital for modeling cell population dynamics.

Purpose of the Study:

  • To quantify the impact of cell-cell interactions on stem cell fate.
  • To investigate how stem cell differentiation probability is influenced by local cellular composition.

Main Methods:

  • Monitoring stem cell differentiation in adherent cultures on precisely sized micropatterns.
  • Collecting statistical cell fate data and analyzing differentiation dynamics using a stochastic model.
  • Investigating the role of epithelial cadherin (E-cadherin) and cell motility.

Main Results:

  • High cell fate variability observed, with bimodal distributions on small micropatterns and unimodal distributions on larger ones.
  • Quantified differentiation probability as a function of stem cell fraction, revealing context-dependent regulation.
  • Demonstrated that stem cells sense and respond to their immediate cellular environment, a process partially mediated by E-cadherin.

Conclusions:

  • Stem cell fate decisions in mixed populations are significantly influenced by stochasticity and cell-cell interactions.
  • Local cellular composition and cell-cell contact play a critical role in modulating stem cell differentiation probability.
  • Cell motility further complicates these dynamics on larger scales, highlighting the complexity of stem cell behavior in vivo.