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Multi-scale Dynamic...
Multi-scale Dynamical Modeling of T Cell Development from an Early Thymic Progenitor State to Lineage Commitment
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- Olariu, Victor (författare)
- Lund University,Lunds universitet,Beräkningsbiologi och biologisk fysik - Har omorganiserats,Institutionen för astronomi och teoretisk fysik - Har omorganiserats,Naturvetenskapliga fakulteten,Computational Biology and Biological Physics - Has been reorganised,Department of Astronomy and Theoretical Physics - Has been reorganised,Faculty of Science
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- Yui, Mary A. (författare)
- California Institute of Technology
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- Krupinski, Pawel (författare)
- Lund University,Lunds universitet,Beräkningsbiologi och biologisk fysik - Har omorganiserats,Institutionen för astronomi och teoretisk fysik - Har omorganiserats,Naturvetenskapliga fakulteten,Computational Biology and Biological Physics - Has been reorganised,Department of Astronomy and Theoretical Physics - Has been reorganised,Faculty of Science
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- Zhou, Wen (författare)
- California Institute of Technology
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- Deichmann, Julia (författare)
- Lund University
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- Andersson, Emil (författare)
- Lund University,Lunds universitet,Beräkningsbiologi och biologisk fysik - Har omorganiserats,Institutionen för astronomi och teoretisk fysik - Har omorganiserats,Naturvetenskapliga fakulteten,Computational Biology and Biological Physics - Has been reorganised,Department of Astronomy and Theoretical Physics - Has been reorganised,Faculty of Science
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- Rothenberg, Ellen V. (författare)
- California Institute of Technology
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- Peterson, Carsten (författare)
- Lund University,Lunds universitet,Beräkningsbiologi och biologisk fysik - Har omorganiserats,Institutionen för astronomi och teoretisk fysik - Har omorganiserats,Naturvetenskapliga fakulteten,Computational Biology and Biological Physics - Has been reorganised,Department of Astronomy and Theoretical Physics - Has been reorganised,Faculty of Science
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- Engelska.
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 34:2
- Relaterad länk:
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http://dx.doi.org/10... (free)
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http://www.cell.com/...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Intrathymic development of committed progenitor (pro)-T cells from multipotent hematopoietic precursors offers an opportunity to dissect the molecular circuitry establishing cell identity in response to environmental signals. This transition encompasses programmed shutoff of stem/progenitor genes, upregulation of T cell specification genes, proliferation, and ultimately commitment. To explain these features in light of reported cis-acting chromatin effects and experimental kinetic data, we develop a three-level dynamic model of commitment based upon regulation of the commitment-linked gene Bcl11b. The levels are (1) a core gene regulatory network (GRN) architecture from transcription factor (TF) perturbation data, (2) a stochastically controlled chromatin-state gate, and (3) a single-cell proliferation model validated by experimental clonal growth and commitment kinetic assays. Using RNA fluorescence in situ hybridization (FISH) measurements of genes encoding key TFs and measured bulk population dynamics, this single-cell model predicts state-switching kinetics validated by measured clonal proliferation and commitment times. The resulting multi-scale model provides a mechanistic framework for dissecting commitment dynamics.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- NATURVETENSKAP -- Fysik -- Annan fysik (hsv//swe)
- NATURAL SCIENCES -- Physical Sciences -- Other Physics Topics (hsv//eng)
Nyckelord
- epigenetic modeling
- experimental validations
- kinetic measurements
- population modeling
- proliferation measurements
- single-cell measurements
- stochastic simulations
- T cell development
- transcriptional modeling
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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