Unbiased Reconstruction of a Mammalian Transcriptional Network Mediating Pathogen Responses
Open accessAbstract
Peeking at Pathogen Response Networks: Networks controlling gene expression serve as key decision-making circuits in cells, but the regulatory networks that control dynamic and specific gene expression responses to stimuli are often not well understood. This is particularly true for immune dendritic cells (DCs), which respond to pathogens by mounting elaborate transcriptional responses, and are centrally involved in infectious diseases, autoimmunity, and vaccines. Amit et al. (p. 257 , published online 3 September) explored the transcriptional response of dendritic cells to specific classes of pathogens. The transcriptional subnetworks responsible for mammalian dendritic cell responses to different pathogens were identified, and the function of 100 regulators clarified.
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Mouse bone marrow-derived dendritic cells are mostly post-mitotic, and LPS synchronizes them and triggers broad regulatory changes.
“DCs are mostly post-mitotic, and LPS synchronizes them (27) and causes dramatic regulatory changes from the expression of thousands of transcripts (22, 24, 25) to protein phosphorylation (26).”
From Dynamic profiling of the protein life cycle in response to pathogens (2015) · cites this paper as [24]
Most prior mammalian regulatory circuit reconstruction studies assumed a single fixed network.
“Most of these studies have relied upon computational circuit-reconstruction algorithms that assume one ‘fixed’ network.”
From Dynamic regulatory network controlling TH17 cell differentiation (2013) · cites this paper as [6]
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- Authors
- Amit, I., Garber, M., Chevrier, N., Leite, A. P., Donner, Y., Eisenhaure, T., Guttman, M., Grenier, J. K., Li, W., Zuk, O., Schubert, L. A., Birditt, B., Shay, T., Goren, A., Zhang, X., Smith, Z., Deering, R., McDonald, R. C., Cabili, M., Bernstein, B. E., Rinn, J. L., Meissner, A., Root, D. E., Hacohen, N., & Regev, A.
- Affiliations
- Broad Institute (US)
- Harvard University (US)
- Nanostring Technologies (United States) (US)
- Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.
- Corresponding author
- Garber, Manuel
- Chevrier, Nicolas
- Leite, Ana Paula
- Donner, Yoni
- Hacohen, Nir
- Regev, Aviv
- ORCID
- Venue
- Science
- Published
- 2009-10-09
- Volume
- 326
- Issue
- 5950
- Pages
- 257-263
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2879337
- OpenAlex
- W2007222211
- Cited by
- 488
- References
- 30
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 16 · 2023: 15 · 2022: 12 · 2021: 14 · 2020: 16 · 2019: 16 · 2018: 25 · 2017: 34 · 2016: 33 · 2015: 32 · 2014: 50 · 2013: 49 · 2012: 58
- FWCI
- 21.45
- Type
- journal article
- Language
- en
- Open access
- green
- orcid.org
- Licence
- cc-by-nc-sa
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (1dp2od002230-01, DP1OD003958)
- National Institute of Allergy and Infectious Diseases (R21AI071060, R21 AI71060)
- National Center for Research Resources (S10RR026688)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- transcriptional regulatory networks, dendritic cells, pathogen response, transcription factors, chromatin modifiers, RNA-binding proteins, network inference, network perturbation, innate immunity, gene expression regulation, mice
- MeSH terms
- Animals, Bacteria, Dendritic Cells, DNA, Single-Stranded, Gene Expression Regulation, Inflammation, Lipopolysaccharides, Mice, Inbred C57BL, Poly I-C, Transcription Factors, Transcription, Genetic, Viruses, RNA-Binding Proteins, Gene Expression Profiling, Feedback, Physiological, Chromatin Assembly and Disassembly, Toll-Like Receptors, Mice, Gene Regulatory Networks, Lipopeptides
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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