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Decoding the regulatory network of early blood development from single-cell gene expression measurements.
Moignard, Victoria; Woodhouse, Steven; Haghverdi, Laleh; Lilly, Andrew J; Tanaka, Yosuke; Wilkinson, Adam C; Buettner, Florian; Macaulay, Iain C; Jawaid, Wajid; Diamanti, Evangelia; Nishikawa, Shin-Ichi; Piterman, Nir; Kouskoff, Valerie; Theis, Fabian J; Fisher, Jasmin; Göttgens, Berthold.
Afiliação
  • Moignard V; Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, UK.
  • Woodhouse S; Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
  • Haghverdi L; Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, UK.
  • Lilly AJ; Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
  • Tanaka Y; Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.
  • Wilkinson AC; Department of Mathematics, Technische Universität München, Garching, Germany.
  • Buettner F; Cancer Research UK Stem Cell Haematopoiesis Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.
  • Macaulay IC; Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, UK.
  • Jawaid W; Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
  • Diamanti E; Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, Chuo-ku, Kobe, Japan.
  • Nishikawa SI; Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, UK.
  • Piterman N; Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
  • Kouskoff V; Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.
  • Theis FJ; Sanger Institute-EBI Single Cell Genomics Centre, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
  • Fisher J; Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, UK.
  • Göttgens B; Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, UK.
Nat Biotechnol ; 33(3): 269-276, 2015 Mar.
Article em En | MEDLINE | ID: mdl-25664528
Reconstruction 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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Sanguíneas / Regulação da Expressão Gênica / Redes Reguladoras de Genes / Análise de Célula Única Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Sanguíneas / Regulação da Expressão Gênica / Redes Reguladoras de Genes / Análise de Célula Única Idioma: En Ano de publicação: 2015 Tipo de documento: Article