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Decoding the regulatory network of early blood development from single-cell gene expression measurements.
Nat. Biotechnol. 33, 269-276 (2015)
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Embryonic Stem-cell; Yolk-sac; Hematopoietic Development; Definitive Hematopoiesis; Rna-seq; Adult Hematopoiesis; Fate Decisions; Mouse Embryos; Leukemia; Mice
ISSN (print) / ISBN
1087-0156
e-ISSN
1546-1696
Zeitschrift
Nature Biotechnology
Quellenangaben
Band: 33,
Heft: 3,
Seiten: 269-276
Verlag
Nature Publishing Group
Verlagsort
New York, NY
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Computational Biology (ICB)