Maintaining and escaping feedback control in hierarchically organised tissue: a case study of the intestinal epithelium
Summary (1 min read)
Introduction
- Belgyógyászati Osztály és Angiológiai szakrendelés, Kistarcsa Bevezetés: A magas vérnyomásban szenvedők 14%-ánál fordulhat elő perifériás verőérbetegség, közülük 1–3% a krónikus kritikus végtagischaemiában szenvedők aránya.
- A betegek életminősége az EQ-5D index alapján stádiumonként átlagosan 0,66; 0,35; 0,18, az EQ-5D értékek alacsonyabbak a korra illesztett átlaglakosság értékeinél, also known as Eredmények.
- Fontaine szerinti osztályozás I. stádium: panaszmentesség, a betegség műszeres vizsgálattal állapítható meg II.
- A kutatás célja a magyarországi Fontaine II–IV.
- A teszteket 5%-os szignifi kanciaszint mellett végeztük.
A vizsgált populáció alapadatai
- Stádiumú betegek elmúlt 12 hónapra jellemző egészségi állapotát és életminőségét (2. táblázat).
- ***Az átkódolás során a mínusz tartományba eső értékeket 0-ra kódoltuk át.
Életminőség; EQ-5D dimenziók
- Az EQ-5D index öt dimenziója és a Fontaine-stádiumok közötti kapcsolatot ábrázolja a 4. táblázat.
- Táblázat Korrelációs mátrix az életminőség és betegséget jellemző változók között Elmúlt hétre jellemző alsó végtagi fájdalom EQ-5D VAS EQ-5D érték (0–1) Elmúlt hétre jellemző alsó végtagi fájdalom – –0,432* –0,683*.
- Jelentős eltérés volt megfi gyelhető a Fontaine II.
- A kockázati tényezők kutatásunkban nem mutatnak jelentős eltéréseket a stádiumokra osztott betegcsoportokban.
- A keresztmetszeti felmérés módszertani korlátaival is számolnunk kell, ugyanis a keresztmetszeti felmérés pillanatképet ad a betegek adott időpontban érvényes életminőségéről.
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Frequently Asked Questions (16)
Q2. What is the dS(t)/dt of the system?
If both the stem cell283 proliferation rate β and differentiation rate δ are unregulated and hence constant, the authors have284 dS(t)/dt = βS − δS, which for any non-trivial steady-state requires β = δ.
Q3. Why do the authors need to ignore the decaying first term of D(t)?
Because the second term of D(t) grows without bounds, the authors may for sufficiently big values of214 t neglect the decaying first term of D(t).
Q4. How many defects can be obtained from model 1?
Because model 1 may show oscillations during its relaxation, an analytical calculation of720 its defects is theoretically possible, but leads to expressions too complicated to handle and721 meaningfully interpret.
Q5. What is the main reason why the colon epithelium model is so desirable?
Because the differentiated cells are responsible for carrying out the designated function499 of a tissue [1], keeping their density as constant as possible is biologically desirable and500 thus grants systems with indirectly regulated stem cell compartments an advantage – even501 more so in tissues like the intestinal and colon epithelium which are constantly exposed to502 mechanical, chemical and biological insults [9].503504
Q6. What is the effect of a steeper feedback function on the system?
notice that δ0 > 0, δslope > 0 can be made arbitrarily small without ever losing stability and switching to unbounded growth; however, if δ0 exceeds β, the non-trivial steady-state becomes unfeasible and unstable, and the system will always converge to the trivial extinction steady-state (lower two panels). (e) A steeper feedback functions causes stronger and longer oscillations.
Q7. What is the simplest way to determine the basal differentiation rate of stem cells?
For simplicity, the authors chose a piecewise linear function with a positive intercept230 δ0 > 0, denoting the basal differentiation rate of stem cells in the absence of any external231 cues.
Q8. What is the mechanism that controls the differentiation rate of stem cells?
Two of them, namely those where the apoptosis rate of differentiated cells is491 controlled, cannot exhibit homoeostasis, showing that a mechanism controlling cycling stem492 cells is required for stability, be it in the form of controlling their proliferation rate, their493 differentiation rate, or potentially both.
Q9. What is the main reason why the colon model performed worse?
However in case of removing stem cells, the513 colon model very often performed significantly worse since removing stem cells will not514 affect stem cell cycling and stem cell differentiation rates in the colon epithelium model.
Q10. What is the relationship between function slope and oscillatory behaviour of the system?
The relationship between function slope and oscillatory behaviour of the system is a bio-266 logically interesting result, as it suggests that in order to keep the occurring oscillations in267 check, a smaller slope of the feedback function might be desirable.
Q11. What is the interesting avenue for future research?
An interesting avenue for future research lies in the examination of healthy and tumoural56226intestinal epithelial tissue on the single-cell level in order to answer the question, whether563 the authors are indeed able to identify similar cellular subpopulation and differentiation gradients564 in both of them.
Q12. What is the reason for the oscillation of the colon epithelium model?
This makes sense because removing509 stem cells from the colon epithelium model cells will cause stem cells to differentiate more510 slowly.
Q13. what is the asymmetric division of hematopoietic stem cells?
A. Marciniak-Czochra, T. Stiehl, A. D. Ho, W. Jäger, and W. Wagner, Modeling of asymmetric644cell division in hematopoietic stem cells—regulation of self-renewal is essential for efficient645repopulation, Stem cells and development 18, 377 (2009).64629[25]
Q14. What is the way to explain the recovery of the colon epithelium model?
The authors have shown both analytically and by526 exemplary numerical simulations how this enables the model to recover more gracefully from527 perturbations, especially those reducing the number of stem cells.
Q15. What is the simplest way to generalise the results of the colon epithelium?
By means of a Taylor expansion around the steady-state, the authors can also generalise this finding433 to arbitrary decreasing differentiable functions %.434435 Panel (b) of Figure 4 shows some exemplary numerical simulations of their colon epithe-436 lium model for the case of no dedifferentiation (first column), a linear dedifferentiation437 with %0 = 0.5, %slope = −0.01 (second column) and a faster linear dedifferentiation with438 %0 = 0.9, %slope = −0.01.
Q16. Why do the authors have to compare the two models pointwise?
Because the two models have different system parameters (β, δ0 vs. β0, δ) we374 cannot directly compare them pointwise in parameter space like the authors did before.