A focused in situ hybridization screen identifies candidate transcriptional regulators of thymic epithelial cell development and function

Qiaozhi Wei, Brian G. Condie

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Thymic epithelial cells (TECs) are necessary for normal T cell development. Currently, one transcription factor, Foxn1 is known to be necessary for the progression of fetal TEC differentiation. However, some aspects of fetal TEC differentiation occur in Foxn1 mutants, suggesting the existence of additional transcriptional regulators of TEC differentiation. The goal of this study was to identify some of the additional candidate transcription factors that may be involved in the specification and/or differentiation of TECs during fetal development. Methodology/Principal Findings: We identified candidate fetal TEC transcriptional regulators via data and text mining. From our data mining we selected the transcription factors Foxg1, Isl1, Gata3, Nkx2-5, Nkx2-6 and Sox2 for further studies. Whole mount in situ hybridizations confirmed the expression of these transcription factors within subdomains of the third pharyngeal pouch from E9.5-E10.5. By E11.5 days Foxg1 and Isl1 transcripts were the only mRNAs from this group of genes detected exclusively within the thymus domain of the third pouch. Based on this initial in situ hybridization analysis, we focused on defining the expression of Foxg1 and Isl1 during multiple stages of thymus development and TEC differentiation. We found that Foxg1 and Isl1 are specifically expressed in differentiating TECs during fetal and postnatal stages of thymus development. In addition, we found differential expression of Islet1 and Foxn1 within the fetal and postnatal TEC population. Conclusions/Significance: Our studies have identified two developmental transcription factors that are excellent candidate regulators of thymic epithelial cell specification and differentiation during fetal development. Our results suggest that Foxg1 and Isl1 may play a role in the regulation of TEC differentiation during fetal and postnatal stages. Our results also demonstrate heterogeneity of TECs marked by the differential expression of transcription factors, potentially providing new insights into the regulation of TEC differentiation.

Original languageEnglish (US)
Article numbere26795
JournalPLoS One
Volume6
Issue number11
DOIs
StatePublished - Nov 7 2011
Externally publishedYes

Fingerprint

in situ hybridization
In Situ Hybridization
epithelial cells
transcription factors
Epithelial Cells
Cell Differentiation
cell differentiation
Transcription Factors
Thymus
Data Mining
Thymus Gland
fetal development
pouches
Fetal Development
Specifications
T-cells
Data mining
T-lymphocytes
Genes
T-Lymphocytes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

A focused in situ hybridization screen identifies candidate transcriptional regulators of thymic epithelial cell development and function. / Wei, Qiaozhi; Condie, Brian G.

In: PLoS One, Vol. 6, No. 11, e26795, 07.11.2011.

Research output: Contribution to journalArticle

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