Modular transcriptional repertoire and MicroRNA target analyses characterize genomic dysregulation in the thymus of Down syndrome infants

Author(s)

Moreira-Filho, Carlos Alberto ^[1] ; Bando, Silvia Yumi ^[1] ; Bertonha, Fernanda Bernardi ^[1] ; Silva, Filipi Nascimento ^[2] ; Costa, Luciano da Fontoura ^[2] ; Ferreira, Leandro Rodrigues ^[1] ; Furlanetto, Glaucio ^[3] ; Chacur, Paulo ^[3] ; Nogueira Zerbini, Maria Claudia ^[4] ; Carneiro-Sampaio, Magda ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Med, Dept Pediat, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Fis Sao Carlos, Sao Carlos, SP - Brazil

^[3] Inst Dante Pazzanese Cardiol, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Fac Med, Dept Patol, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: ONCOTARGET; v. 7, n. 7, p. 7497-7533, FEB 16 2016.
• Web of Science Citations: 2

Abstract

Trisomy 21-driven transcriptional alterations in human thymus were characterized through gene coexpression network (GCN) and miRNA-target analyses. We used whole thymic tissue - obtained at heart surgery from Down syndrome (DS) and karyotipically normal subjects (CT) - and a network-based approach for GCN analysis that allows the identification of modular transcriptional repertoires (communities) and the interactions between all the system's constituents through community detection. Changes in the degree of connections observed for hierarchically important hubs/genes in CT and DS networks corresponded to community changes. Distinct communities of highly interconnected genes were topologically identified in these networks. The role of miRNAs in modulating the expression of highly connected genes in CT and DS was revealed through miRNA-target analysis. Trisomy 21 gene dysregulation in thymus may be depicted as the breakdown and altered reorganization of transcriptional modules. Leading networks acting in normal or disease states were identified. CT networks would depict the ``canonical{''} way of thymus functioning. Conversely, DS networks represent a ``non-canonical{''} way, i. e., thymic tissue adaptation under trisomy 21 genomic dysregulation. This adaptation is probably driven by epigenetic mechanisms acting at chromatin level and through the miRNA control of transcriptional programs involving the networks' high-hierarchy genes. (AU)

• FAPESP's process: 08/58238-4 - Autoimmunity in children: investigation of the molecular and cellular bases of early onset of autoimmunity
• Grantee: Magda Maria Sales Carneiro-Sampaio
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/50489-9 - Human thymus: development and diseases
• Grantee: Magda Maria Sales Carneiro-Sampaio
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 05/00587-5 - Mesh (graph) modeling and techniques of pattern recognition: structure, dynamics and applications
• Grantee: Roberto Marcondes Cesar Junior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 11/50761-2 - Models and methods of e-Science for life and agricultural sciences
• Grantee: Roberto Marcondes Cesar Junior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 09/53443-1 - Neuroimmunology, functional genomics and neuroimaging: an integrated approach for studying physiopathology and treatment in refractory epilepsy
• Grantee: Carlos Alberto Moreira Filho
• Support Opportunities: Research Projects - Thematic Grants