Adler Miri, Medzhitov Ruslan
Department of Genetics, Silberman Institute of Life Science, Edmond J. Safra Campus, The Hebrew University of Jerusalem, Jerusalem, Israel.
Department of Immunology and Cancer Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
bioRxiv. 2024 Nov 20:2024.11.20.624466. doi: 10.1101/2024.11.20.624466.
During embryogenesis, homogenous groups of cells self-organize into stereotypic spatial and temporal patterns that make up tissues and organs. These emergent patterns are controlled by transcription factors and secreted signals that regulate cellular fate and behaviors through intracellular regulatory circuits and cell-cell communication circuits. However, the principles of these circuits and how their properties are combined to provide the spatio-temporal properties of tissues remain unclear. Here we develop a framework to explore building-block circuits of developmental programs. We use single-cell gene expression data across developmental stages of the human intestine to infer the key intra- and inter-cellular circuits that control developmental programs. We study how these circuits are joined into higher-level hyper-motif circuits and explore their emergent dynamical properties. This framework uncovers design principles of developmental programs and reveals the rules that allow cells to develop robust and diverse patterns.
在胚胎发生过程中,同质细胞群会自我组织成构成组织和器官的刻板时空模式。这些涌现的模式由转录因子和分泌信号控制,它们通过细胞内调节回路和细胞间通信回路调节细胞命运和行为。然而,这些回路的原理以及它们的特性如何组合以提供组织的时空特性仍不清楚。在这里,我们开发了一个框架来探索发育程序的构建模块回路。我们使用跨越人类肠道发育阶段的单细胞基因表达数据来推断控制发育程序的关键细胞内和细胞间回路。我们研究这些回路如何连接成更高层次的超模体回路,并探索它们涌现的动力学特性。这个框架揭示了发育程序的设计原则,并揭示了使细胞能够发育出稳健且多样模式的规则。