Gene expression profiling of thymocytes from conditional knock-out mice (FoxN1-Cre mediated KO of Gpr177)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE69766 | GEO | 2015/11/01
SECONDARY ACCESSION(S): PRJNA286738
REPOSITORIES: GEO
Similar Datasets
Project description:Comparative gene expression profiling of thymocytes at the DP, CD4 SP and CD8 SP stage derived from FoxN1-Gpr177 mice (FoxN1-Cre mediated deletion of (Exon3 of) Gpr177/Wtls) or C57Bl/6N mice as comparison. Objective was to test the influence of TEC-secreted Wnt ligands on the transcriptome of thymocytes at the respective developmental stages. Total RNA extracted from FACS-sorted primary mouse thymocytes. CD4/8 double positive (DP) thymocytes, CD4 single positive (CD4 SP) thymocytes and CD8 single positive (CD8 SP) thymocytes were FACS-sorted from conditional knock-out mice (FoxN1-Gpr177) and C57Bl/6N mice as comparison.
2015-11-01 | E-GEOD-69766 | biostudies-arrayexpress
Project description:FOXN1 is a transcription factor critical for the development of both thymic epithelial cell (TEC) and hair follicle cell (HFC) compartments. However, mechanisms controlling its expression remain poorly understood. To address this question, we performed thorough analyses of the conservation and chromatin status of the Foxn1 locus in different tissues and states, and identified several putative cis-regulatory regions unique to TEC vs. HFC. Furthermore, experiments using genetically modified mice with specific deletions in the Foxn1 locus and additional bioinformatic analyses helped us identify key regions and transcription factors involved in either positive or negative regulation of Foxn1 in both TEC and HFC. Specifically, we identified SIX1 and FOXN1 itself, as key factors inducing Foxn1 expression in embryonic and neonatal TECs. Together, our data provide important mechanistic insights into the transcriptional regulation of the Foxn1 gene in TEC vs. HFC and highlight the role of FOXN1 in its autoregulation
2022-08-03 | GSE198591 | GEO
Project description:FOXN1 is a transcription factor critical for the development of both thymic epithelial cell (TEC) and hair follicle cell (HFC) compartments. However, mechanisms controlling its expression remain poorly understood. To address this question, we performed thorough analyses of the conservation and chromatin status of the Foxn1 locus in different tissues and states, and identified several putative cis-regulatory regions unique to TEC vs. HFC. Furthermore, experiments using genetically modified mice with specific deletions in the Foxn1 locus and additional bioinformatic analyses helped us identify key regions and transcription factors involved in either positive or negative regulation of Foxn1 in both TEC and HFC. Specifically, we identified SIX1 and FOXN1 itself, as key factors inducing Foxn1 expression in embryonic and neonatal TECs. Together, our data provide important mechanistic insights into the transcriptional regulation of the Foxn1 gene in TEC vs. HFC and highlight the role of FOXN1 in its autoregulation
2022-08-03 | GSE192872 | GEO
Project description:FOXN1 is a transcription factor critical for the development of both thymic epithelial cell (TEC) and hair follicle cell (HFC) compartments. However, mechanisms controlling its expression remain poorly understood. To address this question, we performed thorough analyses of the conservation and chromatin status of the Foxn1 locus in different tissues and states, and identified several putative cis-regulatory regions unique to TEC vs. HFC. Furthermore, experiments using genetically modified mice with specific deletions in the Foxn1 locus and additional bioinformatic analyses helped us identify key regions and transcription factors involved in either positive or negative regulation of Foxn1 in both TEC and HFC. Specifically, we identified SIX1 and FOXN1 itself, as key factors inducing Foxn1 expression in embryonic and neonatal TECs. Together, our data provide important mechanistic insights into the transcriptional regulation of the Foxn1 gene in TEC vs. HFC and highlight the role of FOXN1 in its autoregulation
2022-08-03 | GSE192871 | GEO
Project description:The transcription factor FOXN1 is a master regulator of thymic epithelial cell development and function. Here we demonstrate that FOXN1 expression is differentially regulated during organogenesis and participates in multi-molecular nuclear condensates essential for the factor's transcriptional activity. FOXN1's C-terminal sequence regulates the diffusion velocity within these aggregates and modulates the binding to proximal gene regulatory regions. These dynamics are significantly altered in a patient's FOXN1 mutant modified in its C-terminal sequence. This mutant is transcriptionally inactive and acts as a dominant negative factor displacing wild-type FOXN1 from condensates and causing athymia and severe lymphopenia in heterozygotes. Expression of the mutated mouse ortholog, Foxn1, selectively impairs mouse thymic epithelial cell (TEC) differentiation, revealing a gene dose dependency for individual TEC subtypes. We have therefore identified the cause for a primary immunodeficiency disease and determined the mechanism by which this FOXN1 gain-of-function mutant mediates its dominant negative effect.
2021-10-29 | PXD025552 | Pride
Project description:FOXN1 is a transcription factor critical for the development of both thymic epithelial cell (TEC) and hair follicle cell (HFC) compartments. However, mechanisms controlling its expression remain poorly understood. To address this question, we performed thorough analyses of the conservation and chromatin status of the Foxn1 locus in different tissues and states, and identified several putative cis-regulatory regions unique to TEC vs. HFC. Furthermore, experiments using genetically modified mice with specific deletions in the Foxn1 locus and additional bioinformatic analyses helped us identify key regions and transcription factors involved in either positive or negative regulation of Foxn1 in both TEC and HFC. Specifically, we identified SIX1 and FOXN1 itself, as key factors inducing Foxn1 expression in embryonic and neonatal TECs. Together, our data provide important mechanistic insights into the transcriptional regulation of the Foxn1 gene in TEC vs. HFC and highlight the role of FOXN1 in its autoregulation
2022-08-03 | GSE204741 | GEO
Project description:FOXN1 is a transcription factor critical for the development of both thymic epithelial cell (TEC) and hair follicle cell (HFC) compartments. However, mechanisms controlling its expression remain poorly understood. To address this question, we performed thorough analyses of the conservation and chromatin status of the Foxn1 locus in different tissues and states, and identified several putative cis-regulatory regions unique to TEC vs. HFC. Furthermore, experiments using genetically modified mice with specific deletions in the Foxn1 locus and additional bioinformatic analyses helped us identify key regions and transcription factors involved in either positive or negative regulation of Foxn1 in both TEC and HFC. Specifically, we identified SIX1 and FOXN1 itself, as key factors inducing Foxn1 expression in embryonic and neonatal TECs. Together, our data provide important mechanistic insights into the transcriptional regulation of the Foxn1 gene in TEC vs. HFC and highlight the role of FOXN1 in its autoregulation
2022-08-03 | GSE192873 | GEO
Project description:The goal of this study was to document the gene expression profile of FOXN1+ thymic endoderm cells derived from the in vitro differentiation of human pluripotent stem cells. Thymic epithelial cells (TECs) play a critical role in T-cell maturation and tolerance induction. The generation of TECs from in vitro differentiation of human pluripotent stem cells (PSCs) would provide a platform for studying the mechanisms of this interaction and have implications for immune reconstitution. To facilitate analysis of PSC-derived TECs, we generated human embryonic stem cell (hESC) reporter lines in which sequences encoding GFP were targeted to FOXN1, a gene required for TEC development. Using this FOXN1GFP/w line as a read out, we developed a reproducible protocol for generating FOXN1-GFP+ thymic endoderm cells. Transcriptional profiling and flow cytometry identified Integrin-β4 (ITGB4, CD104) and HLA-DR as markers that could be used in combination with EpCAM to selectively purify FOXN1+ TEC progenitors from differentiating cultures of unmanipulated PSCs. Human FOXN1+ TEC progenitors generated from PSCs will facilitate the study of thymus biology and are a valuable resource for future applications in regenerative medicine Human embryonic stem cells were differentiated for 30 days using the protocol described by Soh et al, 2014. The hESCs used in this protocol had been genetically modified by targeting sequences encoding GFP to the FOXN1 locus, thus enabling FOXN1 expressing cells to be identified on the basis of GFP expression. At differentiation day 30, differentiating cells were separated into three fractions using FACS. These fractions were the FOXN1+(GFP+)EpCAM+, FOXN1-(GFP-)EpCAM+, FOXN1-(GFP-)EpCAM-.
2014-05-01 | E-GEOD-56373 | biostudies-arrayexpress
Project description:NSrp70 deficiency (NSRP1f/fCD4Cre) profoundly perturbed the late development of DP thymocytes, leading to a significant reduction of single positive (SP) cells in the thymus and peripheral lymphoid tissues. To gain further insight into how NSrp70 controls thymocyte development from CD69+ DP stage, we performed RNA-seq analysis after sorting CD69+ DP thymocytes from WT and Nsrp1 cKO mice.
2020-06-27 | GSE153389 | GEO
Project description:NSrp70 deficiency (NSRP1f/fCD4Cre) profoundly perturbed the late development of DP thymocytes, leading to a significant reduction of single positive (SP) cells in the thymus and peripheral lymphoid tissues. To gain further insight how NSrp70 controls thymocyte development from DP stage, we performed RNA-seq analysis after sorting DP thymocytes from WT and Nsrp1 cKO mice.
2021-06-15 | GSE168379 | GEO