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Stat and interferon genes identified by network analysis differentially regulate primitive and definitive erythropoiesis.
Greenfest-Allen, Emily; Malik, Jeffrey; Palis, James; Stoeckert, Christian J.
Afiliação
  • Greenfest-Allen E; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. stoec
BMC Syst Biol ; 7: 38, 2013 May 15.
Article em En | MEDLINE | ID: mdl-23675896
ABSTRACT

BACKGROUND:

Hematopoietic ontogeny is characterized by overlapping waves of primitive, fetal definitive, and adult definitive erythroid lineages. Our aim is to identify differences in the transcriptional control of these distinct erythroid cell maturation pathways by inferring and analyzing gene-interaction networks from lineage-specific expression datasets. Inferred networks are strongly connected and do not fit a scale-free model, making it difficult to identify essential regulators using the hub-essentiality standard.

RESULTS:

We employed a semi-supervised machine learning approach to integrate measures of network topology with expression data to score gene essentiality. The algorithm was trained and tested on the adult and fetal definitive erythroid lineages. When applied to the primitive erythroid lineage, 144 high scoring transcription factors were found to be differentially expressed between the primitive and adult definitive erythroid lineages, including all expressed STAT-family members. Differential responses of primitive and definitive erythroblasts to a Stat3 inhibitor and IFNγ in vitro supported the results of the computational analysis. Further investigation of the original expression data revealed a striking signature of Stat1-related genes in the adult definitive erythroid network. Among the potential pathways known to utilize Stat1, interferon (IFN) signaling-related genes were expressed almost exclusively within the adult definitive erythroid network.

CONCLUSIONS:

In vitro results support the computational prediction that differential regulation and downstream effectors of STAT signaling are key factors that distinguish the transcriptional control of primitive and definitive erythroid cell maturation.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Inteligência Artificial / Regulação da Expressão Gênica / Interferons / Biologia Computacional / Eritropoese / Fatores de Transcrição STAT / Redes Reguladoras de Genes Tipo de estudo: Prognostic_studies Limite: Adult / Animals / Humans Idioma: En Revista: BMC Syst Biol Assunto da revista: BIOLOGIA / BIOTECNOLOGIA Ano de publicação: 2013 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Inteligência Artificial / Regulação da Expressão Gênica / Interferons / Biologia Computacional / Eritropoese / Fatores de Transcrição STAT / Redes Reguladoras de Genes Tipo de estudo: Prognostic_studies Limite: Adult / Animals / Humans Idioma: En Revista: BMC Syst Biol Assunto da revista: BIOLOGIA / BIOTECNOLOGIA Ano de publicação: 2013 Tipo de documento: Article