E-GEOD-42518 - High-throughput single cell gene expression analysis in primary blood stem and progenitor cells identifies new links between key transcriptional regulators

Status
Released on 24 April 2013, last updated on 1 May 2013
Organism
Mus musculus
Samples (2)
Protocols (3)
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 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
Experiment type
ChIP-seq 
Contacts
Rebecca Louise Hannah <rlh60@cam.ac.uk>, Anagha Joshi, Berthold Gottgens, Fabian Theis, Fernando Calero-Nieto, Florian Buettner, Gemma Swiers, Iain Macaulay, Judith Schuette, Marella de Bruijn, Rebecca Hannah, Sarah Kinston, Sten E Jacobsen, Vicki Moignard
Citation
Characterization of transcriptional networks in blood stem and progenitor cells using high-throughput single-cell gene expression analysis. Moignard V, Macaulay IC, Swiers G, Buettner F, Sch�tte J, Calero-Nieto FJ, Kinston S, Joshi A, Hannah R, Theis FJ, Jacobsen SE, de Bruijn MF, G�ttgens B. , Europe PMC 23524953
MINSEQE
Exp. designProtocolsFactorsProcessedSeq. reads
Files
Investigation descriptionE-GEOD-42518.idf.txt
Sample and data relationshipE-GEOD-42518.sdrf.txt
Processed data (2)E-GEOD-42518.processed.1.zip, E-GEOD-42518.processed.2.zip
Links