MIT的IRIS模型解码细胞信号通路指纹
麻省理工学院助理教授Pulin Li与研究生Nicholas Hutchins领导的研究发现,每条细胞信号通路都会留下独特的基因活性“指纹”,且同一通路在不同细胞类型中保持一致。他们据此开发的神经网络模型IRIS能根据细胞整体基因活动,推断特定发育阶段哪些信号通路处于开启状态;模型训练数据来自数千个人类胚胎干细胞在六条主要信号通路多种组合下的响应。研究团队在小鼠胚胎原肠胚形成期的单细胞上测试IRIS,模型能预测将发育为心脏、肠道、肌肉和脊髓组织的细胞中信号通路何时何地激活,其预测的肺发育相关信号也在小鼠实验中得到了验证;相关开放获取论文于9月8日发表在Nature Methods。
该方法有望让研究人员重建多种细胞类型的信号历史,而不必在每种细胞类型中逐一绘制每条通路,作者称这可能加速干细胞工程和类器官研究。
As an embryo develops from a small cluster of stem cells, those once “blank slate” cells begin to take on more specialized roles like brain, liver, or muscle cells, and organize themselves into three-dimensional structures such as tissues and organs.
The fate of each cell — what type of specialized cell it will become — depends on which genes are turned on or off in the cell. These patterns of gene activity shape the cell’s structure and function, enabling it to take on a specific role in the body.
But this decision isn’t up to individual cells. They constantly send and receive chemical signals to and from neighboring cells, which help them understand where they are, what stage of development they are in, and what they should become. These messages spread through multi-step sequences called signaling pathways, which translate external signals into specific changes in gene activity in the cell.
For researchers, being able to retrace the sequence of instructions a cell has received would offer a powerful way to understand how tissues develop and how these processes go awry in disease.
#MIT#Whitehead Institute for Biomedical Research#IRIS#Nature Methods#Pulin Li#Nicholas Hutchins