Stochastic model for cell population dynamics quantifies homeostasis in colonic crypts and its disruption in early tumorigenesis
Stochastic model for cell population dynamics quantifies homeostasis in colonic crypts and its disruption in early tumorigenesis
复制标题
细胞群动态随机模型量化了结肠隐窝的稳态及其在早期肿瘤发生中的破坏
DOI：
10.1098/rspb.2023.1020
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Bozic, Ivana
中科院分区：
文献类型：
--
作者：
Mamis, Konstantinos;Zhang, Ruibo;Bozic, Ivana
健康的结肠隐窝如何维持其大小，以及驱动突变如何破坏稳态，这些问题对于理解结直肠肿瘤发生至关重要。我们提出了一个三种类型的随机分支过程，占干细胞，transit-amplifying（TA）和完全分化（FD）的细胞，居住在结肠隐窝的细胞群的动态模型。我们的模型是简单的，在其配方，使我们能够估计所有，但一个模型参数的文献。拟合单个剩余参数，我们发现模型结果与健康人类结肠隐窝的数据吻合得很好，捕获了实验观察到的群体大小的相当大的差异。重要的是，我们的模型预测了健康结肠隐窝中相关参数值的稳态群体。我们发现APC和KRAS突变是导致结直肠癌的最重要的早期改变，导致突变隐窝中稳态群体的增加，与实验结果一致。最后，我们的模型预测了一个简单的条件无限增长的细胞在一个隐窝，对应于结直肠恶性肿瘤。当TA细胞的分裂速率超过其分化速率时，预计会发生这种情况，这对治疗性癌症预防策略具有影响。
The questions of how healthy colonic crypts maintain their size, and how homeostasis is disrupted by driver mutations, are central to understanding colorectal tumorigenesis. We propose a three-type stochastic branching process, which accounts for stem, transit-amplifying (TA) and fully differentiated (FD) cells, to model the dynamics of cell populations residing in colonic crypts. Our model is simple in its formulation, allowing us to estimate all but one of the model parameters from the literature. Fitting the single remaining parameter, we find that model results agree well with data from healthy human colonic crypts, capturing the considerable variance in population sizes observed experimentally. Importantly, our model predicts a steady-state population in healthy colonic crypts for relevant parameter values. We show thatAPCandKRASmutations, the most significant early alterations leading to colorectal cancer, result in increased steady-state populations in mutated crypts, in agreement with experimental results. Finally, our model predicts a simple condition for unbounded growth of cells in a crypt, corresponding to colorectal malignancy. This is predicted to occur when the division rate of TA cells exceeds their differentiation rate, with implications for therapeutic cancer prevention strategies.
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影响因子：
29.4
作者：
Feng Y;Bommer GT;Zhao J;Green M;Sands E;Zhai Y;Brown K;Burberry A;Cho KR;Fearon ER
通讯作者：
Fearon ER
影响因子：
24.5
作者：
W. Wong;N. Mandir;R. Goodlad;B. Wong;S. Garcia;S. Lam;N. Wright
通讯作者：
W. Wong;N. Mandir;R. Goodlad;B. Wong;S. Garcia;S. Lam;N. Wright
计算机模型表明干细胞过度生成与结肠癌的发生有关。
DOI：
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发表时间：
2001
期刊：
Cancer research.
影响因子：
--
作者：
Boman,BM;Fields,JZ;Bonham-Carter,O;Runquist,OA
通讯作者：
Runquist,OA
%20干细胞%20区%20的%20%20小%20肠%20上皮。%20IV.%20效果%20%20切除%2030%%20%20%20小%20肠。
影响因子：
--
作者：
M. Bjerknes;Hazel Cheng
通讯作者：
Hazel Cheng
DOI：
10.1039/c3ib40163d
发表时间：
2014-03
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Carulli AJ;Samuelson LC;Schnell S
通讯作者：
Schnell S