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Characterisation of transcriptional networks in blood stem and progenitor cells using high-throughput single cell gene expression analysis
Cellular decision-making is mediated by a complex interplay of external stimuli with the intracellular environment, in particular transcription factor regulatory networks. Here we have determined the expression of a network of 18 key haematopoietic transcription factors (TFs) in 597 single primary b...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796878/ https://www.ncbi.nlm.nih.gov/pubmed/23524953 http://dx.doi.org/10.1038/ncb2709 |
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author | Moignard, Victoria Macaulay, Iain C. Swiers, Gemma Buettner, Florian Schütte, Judith Calero-Nieto, Fernando J. Kinston, Sarah Joshi, Anagha Hannah, Rebecca Theis, Fabian J. Jacobsen, Sten Eirik de Bruijn, Marella Göttgens, Berthold |
author_facet | Moignard, Victoria Macaulay, Iain C. Swiers, Gemma Buettner, Florian Schütte, Judith Calero-Nieto, Fernando J. Kinston, Sarah Joshi, Anagha Hannah, Rebecca Theis, Fabian J. Jacobsen, Sten Eirik de Bruijn, Marella Göttgens, Berthold |
author_sort | Moignard, Victoria |
collection | PubMed |
description | Cellular decision-making is mediated by a complex interplay of external stimuli with the intracellular environment, in particular transcription factor regulatory networks. Here we have determined the expression of a network of 18 key haematopoietic transcription factors (TFs) in 597 single primary blood stem and progenitor cells isolated from mouse bone marrow. We demonstrate that different stem/progenitor populations are characterised by distinctive TF expression states, and through comprehensive bioinformatic analysis reveal positively and negatively correlated TF pairings, including previously unrecognised relationships between Gata2, Gfi1 and Gfi1b. Validation using transcriptional and transgenic assays confirmed direct regulatory interactions consistent with a regulatory triad in immature blood stem cells, where Gata2 may function to modulate cross-inhibition between Gfi1 and Gfi1b. Single cell expression profiling therefore identifies network states and allows reconstruction of network hierarchies involved in controlling stem cell fate choices, and provides a blueprint for studying both normal development and human disease. |
format | Online Article Text |
id | pubmed-3796878 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-37968782013-10-15 Characterisation of transcriptional networks in blood stem and progenitor cells using high-throughput single cell gene expression analysis Moignard, Victoria Macaulay, Iain C. Swiers, Gemma Buettner, Florian Schütte, Judith Calero-Nieto, Fernando J. Kinston, Sarah Joshi, Anagha Hannah, Rebecca Theis, Fabian J. Jacobsen, Sten Eirik de Bruijn, Marella Göttgens, Berthold Nat Cell Biol Article Cellular decision-making is mediated by a complex interplay of external stimuli with the intracellular environment, in particular transcription factor regulatory networks. Here we have determined the expression of a network of 18 key haematopoietic transcription factors (TFs) in 597 single primary blood stem and progenitor cells isolated from mouse bone marrow. We demonstrate that different stem/progenitor populations are characterised by distinctive TF expression states, and through comprehensive bioinformatic analysis reveal positively and negatively correlated TF pairings, including previously unrecognised relationships between Gata2, Gfi1 and Gfi1b. Validation using transcriptional and transgenic assays confirmed direct regulatory interactions consistent with a regulatory triad in immature blood stem cells, where Gata2 may function to modulate cross-inhibition between Gfi1 and Gfi1b. Single cell expression profiling therefore identifies network states and allows reconstruction of network hierarchies involved in controlling stem cell fate choices, and provides a blueprint for studying both normal development and human disease. 2013-03-24 2013-04 /pmc/articles/PMC3796878/ /pubmed/23524953 http://dx.doi.org/10.1038/ncb2709 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Moignard, Victoria Macaulay, Iain C. Swiers, Gemma Buettner, Florian Schütte, Judith Calero-Nieto, Fernando J. Kinston, Sarah Joshi, Anagha Hannah, Rebecca Theis, Fabian J. Jacobsen, Sten Eirik de Bruijn, Marella Göttgens, Berthold Characterisation of transcriptional networks in blood stem and progenitor cells using high-throughput single cell gene expression analysis |
title | Characterisation of transcriptional networks in blood stem and progenitor cells using high-throughput single cell gene expression analysis |
title_full | Characterisation of transcriptional networks in blood stem and progenitor cells using high-throughput single cell gene expression analysis |
title_fullStr | Characterisation of transcriptional networks in blood stem and progenitor cells using high-throughput single cell gene expression analysis |
title_full_unstemmed | Characterisation of transcriptional networks in blood stem and progenitor cells using high-throughput single cell gene expression analysis |
title_short | Characterisation of transcriptional networks in blood stem and progenitor cells using high-throughput single cell gene expression analysis |
title_sort | characterisation of transcriptional networks in blood stem and progenitor cells using high-throughput single cell gene expression analysis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796878/ https://www.ncbi.nlm.nih.gov/pubmed/23524953 http://dx.doi.org/10.1038/ncb2709 |
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