Genomics

Dataset Information

239

High-throughput single cell gene expression analysis in primary blood stem and progenitor cells identifies new links between key transcriptional regulators


ABSTRACT: 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 novel 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. Examination of Gata2 and Gfi1 binding patterns in murine mast cells

ORGANISM(S): Mus musculus  

SUBMITTER: Rebecca Hannah   Judith Schuette  Vicki Moignard  Sten E Jacobsen  Rebecca Louise Hannah  Florian Buettner  Iain Macaulay  Anagha Joshi  Fernando Calero-Nieto  Berthold Gottgens  Sarah Kinston  Marella de Bruijn  Fabian Theis  Gemma Swiers 

PROVIDER: E-GEOD-42518 | ArrayExpress | 2013-04-24

SECONDARY ACCESSION(S): SRP017312GSE42518PRJNA182188

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Characterization of transcriptional networks in blood stem and progenitor cells using high-throughput single-cell gene expression analysis.

Moignard Victoria V   Macaulay Iain C IC   Swiers Gemma G   Buettner Florian F   Schütte Judith J   Calero-Nieto Fernando J FJ   Kinston Sarah S   Joshi Anagha A   Hannah Rebecca R   Theis Fabian J FJ   Jacobsen Sten Eirik SE   de Bruijn Marella F MF   Göttgens Berthold B  

Nature cell biology 20130324 4


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 in 597 single primary blood stem and progenitor cells isolated from mouse bone marrow. We demonstrate that different stem/progenitor populations are characterized by distinctive transcription factor expression states, and through  ...[more]

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