Multistability and predominant hybrid phenotypes in a four node mutually repressive network of Th1/Th2/Th17/Treg differentiation

被引：3

作者：

Duddu, Atchuta Srinivas ^{[1
]}

Andreas, Elizabeth ^{[2
]}

Harshavardhan, B., V ^{[1
,3
]}

Grover, Kaushal ^{[4
]}

Singh, Vivek Raj ^{[5
]}

Hari, Kishore ^{[1
,6
,7
]}

Jhunjhunwala, Siddharth ^{[1
]}

Cummins, Breschine ^{[2
]}

Gedeon, Tomas ^{[2
]}

Jolly, Mohit Kumar ^{[1
]}

机构：

[1] Indian Inst Sci, Dept Bioengn, Bangalore 560012, India

[2] Montana State Univ, Dept Math Sci, Bozeman, MT 59717 USA

[3] Indian Inst Sci, IISc Math Initiat, Bangalore 560012, India

[4] Jawaharlal Nehru Univ, Sch Computat & Integrat Sci, New Delhi 110067, India

[5] Indian Inst Sci, Undergraduate Program, Bangalore 560012, India

[6] Northeastern Univ, Dept Phys, Boston, MA 02115 USA

[7] Northeastern Univ, Ctr Theoret Biol Phys, Boston, MA 02115 USA

来源：

NPJ SYSTEMS BIOLOGY AND APPLICATIONS | 2024年 / 10卷 / 01期

关键词：

REGULATORY T-CELLS; TH2; DIFFERENTIATION; TOGGLE SWITCH; FOXP3; BLIMP-1; EXPRESSION; STABILITY; DYNAMICS; LINEAGE; SERIES;

D O I：

10.1038/s41540-024-00433-6

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Elucidating the emergent dynamics of cellular differentiation networks is crucial to understanding cell-fate decisions. Toggle switch - a network of mutually repressive lineage-specific transcription factors A and B - enables two phenotypes from a common progenitor: (high A, low B) and (low A, high B). However, the dynamics of networks enabling differentiation of more than two phenotypes from a progenitor cell has not been well-studied. Here, we investigate the dynamics of a four-node network A, B, C, and D inhibiting each other, forming a toggle tetrahedron. Our simulations show that this network is multistable and predominantly allows for the co-existence of six hybrid phenotypes where two of the nodes are expressed relatively high as compared to the remaining two, for instance (high A, high B, low C, low D). Finally, we apply our results to understand na & iuml;ve CD4+ T cell differentiation into Th1, Th2, Th17 and Treg subsets, suggesting Th1/Th2/Th17/Treg decision-making to be a two-step process.

引用

页数：12

共 61 条

[1] On logical bifurcation diagrams [J].