scholarly journals Optimal structure of heterogeneous stem cell niche: The importance of cell migration in delaying tumorigenesis

2016 ◽  
Author(s):  
Leili Shahriyari ◽  
Ali Mahdipour–Shirayeh

AbstractStudying the stem cell niche architecture is a crucial step for investigating the process of oncogenesis and obtaining an effective stem cell therapy for various cancers. Recently, it has been observed that there are two groups of stem cells in the stem cell niche collaborating with each other to maintain tissue homeostasis. One group comprises the border stem cells, which is responsible to control the number of non-stem cells as well as stem cells. The other group, central stem cells, regulates the stem cell niche. In the present study, we develop a bi-compartmental stochastic model for the stem cell niche to study the spread of mutants within the niche. The analytic calculations and numeric simulations, which are in perfect agreement, reveal that in order to delay the spread of mutants in the stem cell niche, a small but non-zero number of stem cell proliferations must occur in the central stem cell compartment. Moreover, the migration of border stem cells to the central stem cell compartment delays the spread of mutants. Furthermore, the fixation probability of mutants in the stem cell niche is independent of types of stem cell division as long as all stem cells do not divide fully asymmetrically. Additionally, the progeny of central stem cells have a much higher chance than the progeny of border stem cells to take over the entire niche.

2020 ◽  
Vol 71 (2) ◽  
pp. 211-213
Author(s):  
K. Sato ◽  
S. Chitose ◽  
K. Sato ◽  
F. Sato ◽  
T. Kurita ◽  
...  

2008 ◽  
Vol 8 ◽  
pp. 1168-1176 ◽  
Author(s):  
Laren Becker ◽  
Qin Huang ◽  
Hiroshi Mashimo

Lgr5 has recently been identified as a murine marker of intestinal stem cells. Its expression has not been well characterized in human gastrointestinal tissues, but has been reported in certain cancers. With the increasing appreciation for the role of cancer stem cells or tumor-initiating cells in certain tumors, we sought to explore the expression of Lgr5 in normal and premalignant human gastrointestinal tissues. Using standard immunostaining, we compared expression of Lgr5 in normal colon and small intestine vs. small intestinal and colonic adenomas and Barrett's esophagus. In the normal tissue, Lgr5 was expressed in the expected stem cell niche, at the base of crypts, as seen in mice. However, in premalignant lesions, Lgr5+cells were not restricted to the crypt base. Additionally, their overall numbers were increased. In colonic adenomas, Lgr5+cells were commonly found clustered at the luminal surface and rarely at the crypt base. Finally, we compared immunostaining of Lgr5 with that of CD133, a previously characterized marker for tumor-initiating cells in colon cancer, and found that they identified distinct subpopulations of cells that were in close proximity, but did not costain. Our findings suggest that (1) Lgr5 is a potential marker of intestinal stem cells in humans and (2) loss of restriction to the stem cell niche is an early event in the premalignant transformation of stem cells and may play a role in carcinogenesis.


2020 ◽  
Author(s):  
Lucía Benítez ◽  
Lucas Barberis ◽  
Luciano Vellón ◽  
Carlos Alberto Condat

Abstract Background: Cancer stem cells are important for the development of many solid tumors. These cells receive promoting and inhibitory signals that depend on the nature of their environment (their niche) and determine cell dynamics. Mechanical stresses are crucial to the initiation and interpretation of these signals. Methods: A two-population mathematical model of tumorsphere growth is used to interpret the results of a series of experiments recently carried out in Tianjin, China, and extract information about the intraspecific and interspecific interactions between cancer stem cell and differentiated cancer cell populations. Results: The model allows us to reconstruct the time evolution of the cancer stem cell fraction, which was not directly measured. We find that, in the presence of stem cell growth factors, the interspecific cooperation between cancer stem cells and differentiated cancer cells induces a positive feedback loop that determines growth, independently of substrate hardness. In a frustrated attempt to reconstitute the stem cell niche, the number of cancer stem cells increases continuously with a reproduction rate that is enhanced by a hard substrate. For growth on soft agar, intraspecific interactions are always inhibitory, but on hard agar the interactions between stem cells are collaborative while those between differentiated cells are strongly inhibitory. Evidence also suggests that a hard substrate brings about a large fraction of asymmetric stem cell divisions. In the absence of stem cell growth factors, the barrier to differentiation is broken and overall growth is faster, even if the stem cell number is conserved. Conclusions: Our interpretation of the experimental results validates the centrality of the concept of stem cell niche when tumor growth is fueled by cancer stem cells. Niche memory is found to be responsible for the characteristic population dynamics observed in tumorspheres. A specific condition for the growth of the cancer stem cell number is also obtained.


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