多细胞生物
生物
细胞命运测定
基因调控网络
基因
转录因子
基因表达调控
基因表达
计算生物学
电池类型
谱系(遗传)
细胞分化
遗传学
细胞
转录调控
细胞生物学
作者
Merja Heinäniemi,Matti Nykter,Roger Kramer,Anke Wienecke-Baldacchino,Lasse Sinkkonen,Joseph Zhou,Richard Kreisberg,Stuart Kauffman,Sui Huang,Ilya Shmulevich
出处
期刊:Nature Methods
[Springer Nature]
日期:2013-04-21
卷期号:10 (6): 577-583
被引量:135
摘要
A method to measure reversals in gene expression between cell types is used to identify transcriptional regulators important for lineage specification. The approach should help identify putative factors for direct fate conversion. The distinct cell types of multicellular organisms arise owing to constraints imposed by gene regulatory networks on the collective change of gene expression across the genome, creating self-stabilizing expression states, or attractors. We curated human expression data comprising 166 cell types and 2,602 transcription-regulating genes and developed a data-driven method for identifying putative determinants of cell fate built around the concept of expression reversal of gene pairs, such as those participating in toggle-switch circuits. This approach allows us to organize the cell types into their ontogenic lineage relationships. Our method identifies genes in regulatory circuits that control neuronal fate, pluripotency and blood cell differentiation, and it may be useful for prioritizing candidate factors for direct conversion of cell fate.
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