Gene regulatory network inference with popInfer reveals dynamic regulation of hematopoietic stem cell quiescence upon diet restriction and aging

Inference of gene regulatory networks (GRNs) can reveal cell state transitions from single-cell genomics data. However, obstacles to temporal inference from snapshot data are difficult to overcome. Single-nuclei multiomics data offer means to bridge this gap and derive temporal information from snapshot data using joint measurements of gene expression and chromatin accessibility in the same single cells. We developed popInfer to infer networks that characterize lineage-specific dynamic cell state transitions from joint gene expression and chromatin accessibility data. Benchmarking against alternative methods for GRN inference, we showed that popInfer achieves higher accuracy in the GRNs inferred. popInfer was applied to study single-cell multiomics data characterizing hematopoietic stem cells (HSCs) and the transition from HSC to a multipotent progenitor cell state during murine hematopoiesis across age and dietary conditions. From networks predicted by popInfer, we discovered gene interactions controlling entry to/exit from HSC quiescence that are perturbed in response to diet or aging.

• Publication year

  2023

• Venue

  bioRxiv

• Publication date

  2023-04-20

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1101/2023.04.18.537360PMID 37131596PMCID 10153203
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2021cited by this paper
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  2020cited by this paper
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  2020cited by this paper
• MLLT3 governs human haematopoietic stem-cell self-renewal and engraftment

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  2019cited by this paper
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  2019cited by this paper
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  2019cited by this paper
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  2019cited by this paper
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  2018cited by this paper
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  2018cited by this paper
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  2018cited by this paper
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  2018cited by this paper
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  2017cited by this paper
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  2017cited by this paper
• SCODE: an efficient regulatory network inference algorithm from single-cell RNA-Seq during differentiation

  2016cited by this paper
• An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability

  2016cited by this paper
• Computational methods for trajectory inference from single‐cell transcriptomics

  2016cited by this paper
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  2016cited by this paper
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  2016cited by this paper
• Single-cell analysis of mixed-lineage states leading to a binary cell fate choice

  2016cited by this paper
• Diffusion pseudotime robustly reconstructs lineage branching

  2016influential reference
• SINCERITIES: inferring gene regulatory networks from time-stamped single cell transcriptional expression profiles

  2016cited by this paper
• Gene Regulatory Network Inference from Single-Cell Data Using Multivariate Information Measures

  2016cited by this paper
• Distinct routes of lineage development reshape the human blood hierarchy across ontogeny

  2016cited by this paper
• Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors.

  2015cited by this paper
• Defining cell types and states with single-cell genomics

  2015cited by this paper
• Hematopoietic stem cell niche maintenance during homeostasis and regeneration

  2014cited by this paper
• The bone marrow niche for haematopoietic stem cells

  2014cited by this paper
• Activation of Evi1 inhibits cell cycle progression and differentiation of hematopoietic progenitor cells

  2013cited by this paper
• The hallmarks of aging.

  2013cited by this paper
• Hematopoietic Stem and Progenitor Cells Acquire Distinct DNA-Hypermethylation During in vitro Culture

  2013cited by this paper
• All hematopoietic cells develop from hematopoietic stem cells through Flk2/Flt3-positive progenitor cells.

  2011cited by this paper
• Tracking single hematopoietic stem cells in vivo using high-throughput sequencing in conjunction with viral genetic barcoding

  2011cited by this paper
• Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment

  2010cited by this paper
• Inferring Regulatory Networks from Expression Data Using Tree-Based Methods

  2010cited by this paper
• Regularization Paths for Generalized Linear Models via Coordinate Descent.

  2010cited by this paper
• Accurate Whole Human Genome Sequencing using Reversible Terminator Chemistry

  2008cited by this paper
• Bifurcation dynamics in lineage-commitment in bipotent progenitor cells.

  2007cited by this paper
• Regression Shrinkage and Selection via the Lasso

  1996cited by this paper

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  2025cites this paper
• Hematopoietic stem cell aging by the niche.

  2024cites this paper