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单细胞分辨率下胚胎发育的连续统。

The continuum of embryonic development at single-cell resolution.

机构信息

Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.

The Crown Genomics Institute of the Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.

出版信息

Science. 2022 Aug 5;377(6606):eabn5800. doi: 10.1126/science.abn5800.

Abstract

is a powerful, long-standing model for metazoan development and gene regulation. We profiled chromatin accessibility in almost 1 million and gene expression in half a million nuclei from overlapping windows spanning the entirety of embryogenesis. Leveraging developmental asynchronicity within embryo collections, we applied deep neural networks to infer the age of each nucleus, resulting in continuous, multimodal views of molecular and cellular transitions in absolute time. We identify cell lineages; infer their developmental relationships; and link dynamic changes in enhancer usage, transcription factor (TF) expression, and the accessibility of TFs' cognate motifs. With these data, the dynamics of enhancer usage and gene expression can be explored within and across lineages at the scale of minutes, including for precise transitions like zygotic genome activation.

摘要

是一种强大的、历史悠久的后生动物发育和基因调控模型。我们对来自胚胎发生全过程重叠窗口的近 100 万个核的染色质可及性和 50 万个核的基因表达进行了分析。利用胚胎集合内的发育异步性,我们应用深度神经网络来推断每个核的年龄,从而在绝对时间内连续、多模式地观察分子和细胞的转变。我们鉴定细胞谱系;推断它们的发育关系;并将增强子使用、转录因子 (TF) 表达以及 TF 同源基序的可及性的动态变化联系起来。有了这些数据,就可以在谱系内和谱系间以分钟为单位探索增强子使用和基因表达的动态,包括像合子基因组激活这样的精确转变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7ca/9371440/3054fc221438/nihms-1828489-f0001.jpg

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