Cited by 670Genomics and Chromatin DynamicsSingle-cell and spatial transcriptomicsGene Regulatory Network Analysis

Integrated Single-Cell Analysis Maps the Continuous Regulatory Landscape of Human Hematopoietic Differentiation

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Buenrostro, Jason D., Corces, M. Ryan, Lareau, Caleb A., Wu, Beijing, Schep, Alicia N., Aryee, Martin J., Majeti, Ravindra, Chang, Howard Y. +1 more·2018·Cell

Abstract

Human hematopoiesis involves cellular differentiation of multipotent cells into progressively more lineage-restricted states. While the chromatin accessibility landscape of this process has been explored in defined populations, single-cell regulatory variation has been hidden by ensemble averaging. We collected single-cell chromatin accessibility profiles across 10 populations of immunophenotypically defined human hematopoietic cell types and constructed a chromatin accessibility landscape of human hematopoiesis to characterize differentiation trajectories. We find variation consistent with lineage bias toward different developmental branches in multipotent cell types. We observe heterogeneity within common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs) and develop a strategy to partition GMPs along their differentiation trajectory. Furthermore, we integrated single-cell RNA sequencing (scRNA-seq) data to associate transcription factors to chromatin accessibility changes and regulatory elements to target genes through correlations of expression and regulatory element accessibility. Overall, this work provides a framework for integrative exploration of complex regulatory dynamics in a primary human tissue at single-cell resolution.

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Crossref · 10.1016/j.cell.2018.03.074

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  • ATAC-seq can be performed in single cells, revealing cell-to-cell variability and rare epigenomic phenotypes.

    “Importantly, ATAC-seq can be performed in single cells (scATAC-seq), uncovering cell-to-cell variability and rare epigenomic phenotypes (Cusanovich et al., 2018; Satpathy et al., 2018; Buenrostro et al., 2018).”
  • Single-cell measurements of transcriptional states, chromatin accessibility, and DNA methylation have provided a better understanding of heterogeneity in regulatory mechanisms during hematopoiesis.

    “Single-cell measurements of transcriptional states, chromatin accessibility, and DNA methylation, have also provided a better understanding of the heterogeneity that exists in such regulatory mechanisms during hematopoiesis (Buenrostro et al., 2018; Cao et al., 2018; Ludwig et al., 2019b; Ulirsch et al., 2019).”

    From Unraveling Hematopoiesis through the Lens of Genomics (2020) · cites this paper as Buenrostro et al., 2018

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Authors
Buenrostro, J. D., Corces, M. R., Lareau, C. A., Wu, B., Schep, A. N., Aryee, M. J., Majeti, R., Chang, H. Y., & Greenleaf, W. J.
Affiliations
  • Broad Institute (US)
  • Stanford University (US)
  • Stanford Medicine (US)
  • Chan Zuckerberg Biohub San Francisco (US)
Corresponding author
  • Buenrostro, Jason D.
  • Greenleaf, William J.
Venue
Cell
Publisher
Elsevier BV
Published
2018-05
Volume
173
Issue
6
Pages
1535-1548.e16
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2801527818
Cited by
670
References
54
Citations by year
2026: 50 · 2025: 63 · 2024: 74 · 2023: 87 · 2022: 96 · 2021: 108 · 2020: 94 · 2019: 68 · 2018: 28 · 2017: 1
FWCI
27.30
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIH (P50HG007735, UM1HG009442, U19AI057266)
  • Stinehart-Reed Foundation
  • Rita Allen Foundation
  • Baxter Foundation Faculty Scholar Grant
  • Human Frontiers Science Program (RGY006S)
  • Chan Zuckerberg Initiative (2017-174468, 2018-182817)
  • Harvard Society of Fellows
  • Broad Institute Fellowship
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
Keywords
hematopoiesis, hematopoietic differentiation, chromatin accessibility, common myeloid progenitors, CFU-GM, lineage bias, differentiation trajectories, transcription factors, regulatory elements
MeSH terms
Animals, Cell Differentiation, Chromatin, Gene Expression Regulation, Hematopoiesis, Hematopoietic Stem Cells, Humans, Regulatory Sequences, Nucleic Acid, Transcription Factors, Sequence Analysis, RNA, Hematopoietic Stem Cell Transplantation, Cell Lineage, Myeloid Progenitor Cells, Principal Component Analysis, Epigenesis, Genetic, Epigenomics, Single-Cell Analysis, Transcriptome

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