Cited by 384Gene Regulatory Network AnalysisSingle-cell and spatial transcriptomicsDevelopmental Biology and Gene Regulation

The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.

Decoding the regulatory network of early blood development from single-cell gene expression measurements

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Abstract

Reconstruction of the molecular pathways controlling organ development has been hampered by a lack of methods to resolve embryonic progenitor cells. Here we describe a strategy to address this problem that combines gene expression profiling of large numbers of single cells with data analysis based on diffusion maps for dimensionality reduction and network synthesis from state transition graphs. Applying the approach to hematopoietic development in the mouse embryo, we map the progression of mesoderm toward blood using single-cell gene expression analysis of 3,934 cells with blood-forming potential captured at four time points between E7.0 and E8.5. Transitions between individual cellular states are then used as input to develop a single-cell network synthesis toolkit to generate a computationally executable transcriptional regulatory network model of blood development. Several model predictions concerning the roles of Sox and Hox factors are validated experimentally. Our results demonstrate that single-cell analysis of a developing organ coupled with computational approaches can reveal the transcriptional programs that underpin organogenesis.

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Metadata

Authors
Moignard, V., Woodhouse, S., Haghverdi, L., Lilly, A. J., Tanaka, Y., Wilkinson, A. C., Buettner, F., Macaulay, I. C., Jawaid, W., Diamanti, E., Nishikawa, S.-I., Piterman, N., Kouskoff, V., Theis, F. J., Fisher, J., & Göttgens, B.
Affiliations
  • Wellcome/MRC Cambridge Stem Cell Institute (GB)
  • Helmholtz Munich (DE)
  • Cancer Research UK (GB)
  • Wellcome Sanger Institute (GB)
  • University of Cambridge (GB)
  • RIKEN (JP)
  • University of Leicester (GB)
Corresponding author
  • Theis, Fabian J
  • Fisher, Jasmin
  • Göttgens, Berthold
Venue
Nature Biotechnology
Published
2015-02-09
Volume
33
Issue
3
Pages
269-276
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
OpenAlex
W2136453810
Cited by
380
References
58
Citations by year
2026: 8 · 2025: 11 · 2024: 24 · 2023: 26 · 2022: 29 · 2021: 30 · 2020: 45 · 2019: 38 · 2018: 42 · 2017: 50 · 2016: 51 · 2015: 25
FWCI
24.30
Type
journal article
Language
en
Open access
Locations
  • Nature Biotechnology (publishedVersion)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Apollo (University of Cambridge) (acceptedVersion)
  • Leicester Research Archive (University of Leicester) (submittedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
  • Site cant be reached (submittedVersion)
  • PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
Funders
  • Leukemia and Lymphoma Society
  • Microsoft Research
  • Wellcome Trust (100140, 97922, 097922)
  • Cancer Research UK (12486, 12765)
  • Leukaemia and Lymphoma Research
  • Medical Research Council (MR/M008975/1, MC_PC_12009)
  • Biotechnology and Biological Sciences Research Council (BB/I00050X/1)
  • Cambridge Institute for Medical Research, University of Cambridge
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
hematopoietic development, transcriptional regulatory networks, single-cell gene expression, diffusion maps, state diagrams, network synthesis, organogenesis, mouse embryo
MeSH terms
Animals, Base Sequence, Blood Cells, Computer Simulation, Diffusion, Female, Gene Expression Regulation, Male, Mice, Inbred ICR, Models, Genetic, Molecular Sequence Data, Transcription, Genetic, Gene Expression Profiling, Gene Regulatory Networks, Gastrulation, Single-Cell Analysis

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