Transcriptional and post-transcriptional activity of thymocytes adhered to Aire mutant mTEC cells

• Grant number: 20/09664-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: January 01, 2021
• End date: December 31, 2023
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Geraldo Aleixo da Silva Passos Júnior
• Grantee: Mayara Cristina Vieira Machado
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 17/10780-4 - Effect of CRISPR-Cas9-induced mutations in the Aire gene (APS1 syndrome) on protein conformation, mTEC cell transcriptome and their interaction with thymocytes, AP.TEM

Abstract

The fellow will study the transcriptional profile involving mRNAs and miRNAs of thymocytes that physically interact with Aire wild-type (wt) or Aire mutant mTECs cells (adhesion mTECs-thymocytes in vitro). As discussed in the thematic project, the interaction between thymocytes and epithelial thymic cells (TECs) is essential for the development of these two cell types. To test this hypothesis, we will use the mTEC-thymocyte adhesion model system (in vitro co-culture) to study its effect on the modulation of gene expression. As we have already seen that this type of adherence interferes with the mTEC transcriptome (Pezzi et al 2016), we raised the possibility that this may also influence the transcriptional activity of thymocytes. We will test whether mutations in the Aire gene associated with the APS1 syndrome, but induced by the CRISPR-Cas9 system (mutations of the human Aire gene in the SAND and PHD1 domains) in mTECs, may influence adherence and, consequently, the transcriptional activity of thymocytes. Once with the expression data from thymocytes that adhered to Aire wt or Aire mutant mTEC cells, we will investigate the interaction networks between these two RNA species, that is, the miRNAs-mRNA interactions that ultimately control gene expression at post-transcriptional level. The results will be useful to assess whether there is an association between Aire mutations in mTECs with the gene activity of thymocytes that adhere to these cells, which is also important for the establishment of immunological tolerance. (AU)

Scientific publications

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

MONTEIRO, CINTIA J.; DUARTE, MAX J.; MACHADO, MAYARA CRISTINA V.; MASCARENHAS, ROMARIO S.; PALMA, PATRICIA V. BONINI; GARCIA, HENRY D. MOGOLLON; NAKAYA, HELDER I.; CUNHA, THIAGO M.; DONADI, EDUARDO A.; PASSOS, GERALDO A.. The single-cell transcriptome of mTECs and CD4⁺ thymocytes under adhesion revealed heterogeneity of mTECs and a network controlled by Aire and lncRNAs. FRONTIERS IN IMMUNOLOGY, v. 15, p. 18-pg., 2024-08-26. (18/14933-2, 20/09664-2, 21/02081-4, 17/10780-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MACHADO, Mayara Cristina Vieira. The pervasiveness of the del 3554G mutation in exon 6 (SAND domain) of the Aire gene affects the transcriptome of medullary thymic epithelial cells and adherent CD4+ thymocytes. 2024. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.