Mapping transcriptomic vector fields of single cells.
Mapping transcriptomic vector fields of single cells.
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DOI：
10.1016/j.cell.2021.12.045
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发表时间：
2022-02-17
期刊：
影响因子：
64.5
通讯作者：
Weissman, Jonathan S.
中科院分区：
文献类型：
--
作者：
Qiu, Xiaojie;Zhang, Yan;Martin-Rufino, Jorge D.;Weng, Chen;Hosseinzadeh, Shayan;Yang, Dian;Pogson, Angela N.;Hein, Marco Y.;Min, Kyung Hoi (Joseph);Wang, Li;Grody, Emanuelle, I;Shurtleff, Matthew J.;Yuan, Ruoshi;Xu, Song;Ma, Yian;Replogle, Joseph M.;Lander, Eric S.;Darmanis, Spyros;Bahar, Ivet;Sankaran, Vijay G.;Xing, Jianhua;Weissman, Jonathan S.
单细胞（sc）-RNA-seq与RNA速度和代谢标记一起，以前所未有的分辨率揭示细胞状态和转换。然而，充分利用这些数据，需要动力学模型能够揭示管理监管功能。在这里，我们介绍了一个分析框架发电机，推断绝对RNA速度，重建连续向量场函数预测细胞命运，采用微分几何提取潜在的法规，并最终预测最佳的重编程路径和扰动结果。我们强调了dynamo克服传统基于剪接的RNA速度分析的基本局限性的能力，以实现对代谢标记的人类造血scRNA-seq数据集的准确速度估计。此外，微分几何分析揭示了机制驱动早期巨核细胞的外观和阐明不对称调节内的PU.1-GATA 1电路。利用最小行动路径方法，dynamo准确地预测了许多造血转变的驱动因素。最后，在硅片扰动预测基因扰动诱导的细胞命运转移。因此，Dynamo代表了推进细胞状态转变的定量和预测理论的重要一步。
Single-cell (sc)-RNA-seq, together with RNA-velocity and metabolic labeling, reveals cellular states and transitions at unprecedented resolution. Fully exploiting these data, however, requires kinetic models capable of unveiling governing regulatory functions. Here, we introduce an analytical framework dynamo, that infers absolute RNA velocity, reconstructs continuous vector-field functions that predict cell fates, employs differential geometry to extract underlying regulations, and ultimately predicts optimal reprogramming paths and perturbation outcomes. We highlight dynamo’s power to overcome fundamental limitations of conventional splicing-based RNA velocity analyses to enable accurate velocity estimations on a metabolically-labeled human hematopoiesis scRNA-seq dataset. Furthermore, differential geometry analyses reveal mechanisms driving early megakaryocyte appearance and elucidate asymmetrical regulation within the PU.1–GATA1 circuit. Leveraging the Least-Action-Path method, dynamo accurately predicts drivers of numerous hematopoietic transitions. Finally, in silico perturbations predict cell-fate diversions induced by gene perturbations. Dynamo thus represents an important step in advancing quantitative and predictive theories of cell-state transitions.
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影响因子：
8.8
作者：
Capellera-Garcia S;Pulecio J;Dhulipala K;Siva K;Rayon-Estrada V;Singbrant S;Sommarin MN;Walkley CR;Soneji S;Karlsson G;Raya Á;Sankaran VG;Flygare J
通讯作者：
Flygare J
影响因子：
24.8
作者：
Drissen, Roy;Thongjuea, Supat;Nerlov, Claus
通讯作者：
Nerlov, Claus
影响因子：
56.9
作者：
Battich, Nico;Beumer, Joep;van Oudenaarden, Alexander
通讯作者：
van Oudenaarden, Alexander
影响因子：
64.5
作者：
Dixit, Atray;Pamas, Oren;Li, Biyu;Chen, Jenny;Fulco, Charles P.;Jerby-Amon, Livnat;Marjanovic, Nemanja D.;Dionne, Danielle;Burks, Tyler;Raychowdhury, Raktima;Adamson, Britt;Norman, Thomas M.;Lander, Eric S.;Weissman, Jonathan S.;Friedman, Nir;Regev, Aviv
通讯作者：
Regev, Aviv
影响因子：
64.8
作者：
Tabula Muris Consortium
通讯作者：
Tabula Muris Consortium