5/29, LSBM Monday Seminar Series #22, Kenji Kamimoto, Dissecting cell identity via network inference and in silico gene perturbation

Presenter: Kenji Kamimoto

Affiliation: Senior Researcher, Samantha Morris Lab, Department of Developmental Biology and Genetics, Washington University in St.Louis, USA

Title: Dissecting cell identity via network inference and in silico gene perturbation

 

 

Abstract: Recent technological advances in single-cell sequencing enable the acquisition of multi-dimensional data in a high-throughput manner. These technologies reveal the existence of heterogeneity and the diversity of cell states and identities. To dissect the regulatory mechanisms underlying such phenomena, many computational methods to infer Gene regulatory Networks (GRNs) have been proposed. However, understanding biological events from a GRN perspective remains difficult. Even if a computational algorithm can infer GRN models, the biological network is so complex that it is challenging to understand how it systematically dictates cell identities. There is significant demand for new methodologies that bridge the gap between cellular phenotypes and the underlying GRN model. Thus, we have developed a new computational method, CellOracle, for the inference and analysis of GRNs. CellOracle first infers sample-specific GRN configurations from single-cell RNA-seq and ATAC-seq data by utilizing machine learning algorithms and genetic information. Our GRN models are designed to be used for the simulation of cell identity changes in response to gene perturbation. This simulation enables network configurations to be interrogated in relation to cell-fate regulation, facilitating their interpretation. We validate the efficacy of CellOracle to recapitulate known outcomes of well-characterized gene perturbations in developmental processes, including mouse and human hematopoiesis. We also apply CellOracle to zebrafish embryogenesis, systematically perturbing transcription factors and experimentally validating key candidates, identifying a novel mechanism that regulates cell identity in axial mesoderm development. Our validation results demonstrate the efficacy of our new approach to infer and interpret the dynamics of GRN configurations, promoting new mechanistic insights into the regulation of cell identity.

 

 

References:

  1. Kamimoto, K et al., Dissecting cell identity via network inference and in silico gene perturbation. Nature, 2023
  2. Kamimoto, K et al., Gene regulatory network reconfiguration in direct lineage reprogramming. Stem Cell Reports, 2023

 

[略歴]

2012年 東京大学理学部生物化学科 卒業

2017年 東京大学理学系研究科生物科学科 博士課程修了(宮島篤 教授)

2017年 東京大学 分子細胞生物学研究所 先導的研究教育プログラム助教

2017年 Post-Doctoral Researcher, Samantha Morris Lab, Department of Developmental Biology and Genetics, Washington University in St.Louis, USA

2022年 Senior Researcher, Samantha Morris Lab, Department of Developmental Biology and Genetics, Washington University in St.Louis, USA

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