Decoding the regulatory network of early blood development from single-cell gene expression measurements.
Lilly, A J
AffiliationDepartment of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
MetadataShow full item record
AbstractReconstruction of the molecular pathways controlling organ development has been hampered by a lack of methods to resolve embryonic progenitor cells. Here we describe a strategy to address this problem that combines gene expression profiling of large numbers of single cells with data analysis based on diffusion maps for dimensionality reduction and network synthesis from state transition graphs. Applying the approach to hematopoietic development in the mouse embryo, we map the progression of mesoderm toward blood using single-cell gene expression analysis of 3,934 cells with blood-forming potential captured at four time points between E7.0 and E8.5. Transitions between individual cellular states are then used as input to develop a single-cell network synthesis toolkit to generate a computationally executable transcriptional regulatory network model of blood development. Several model predictions concerning the roles of Sox and Hox factors are validated experimentally. Our results demonstrate that single-cell analysis of a developing organ coupled with computational approaches can reveal the transcriptional programs that underpin organogenesis.
CitationDecoding the regulatory network of early blood development from single-cell gene expression measurements. 2015: Nat Biotechnol
- Predictive regulatory models in Drosophila melanogaster by integrative inference of transcriptional networks.
- Authors: Marbach D, Roy S, Ay F, Meyer PE, Candeias R, Kahveci T, Bristow CA, Kellis M
- Issue date: 2012 Jul
- An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability.
- Authors: Schütte J, Wang H, Antoniou S, Jarratt A, Wilson NK, Riepsaame J, Calero-Nieto FJ, Moignard V, Basilico S, Kinston SJ, Hannah RL, Chan MC, Nürnberg ST, Ouwehand WH, Bonzanni N, de Bruijn MF, Göttgens B
- Issue date: 2016 Feb 22
- Singling out blood development.
- Authors: Fast EM, Zon LI
- Issue date: 2015 Mar
- Single-cell analysis of mixed-lineage states leading to a binary cell fate choice.
- Authors: Olsson A, Venkatasubramanian M, Chaudhri VK, Aronow BJ, Salomonis N, Singh H, Grimes HL
- Issue date: 2016 Sep 29
- Transcriptional hierarchies regulating early blood cell development.
- Authors: Moignard V, Woodhouse S, Fisher J, Göttgens B
- Issue date: 2013 Dec