Thymic alveolar type II epithelial mimetic cells revealed by Runx1-deficiency [scRNA-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE290144 | GEO | 2026/04/23
REPOSITORIES: GEO
Similar Datasets
Project description:The mechanisms used to prevent autoimmune lung disease are incompletely understood. Recent studies in the thymus have identified unique populations of medullary thymic epithelial cells (mTECs) called mimetic cells that transcriptionally mimic peripheral epithelial populations. These mimetic cells have been found to have important functions in the thymus in immune tolerance and the diversity and cell types represented in this pool of cells represents an active area of investigation. Here, we utilized a mouse line with thymic specific deletion of the Runt related transcription factor 1 (Runx1) to identify a novel mimetic cell type that transcriptionally mimic alveolar type II (AT2) lung epithelial cells. Runx1 binds to genomic regions associated with epidermal growth factor receptor (EGFR) signaling suggesting a function for EGFR in regulating AT2 mTEC development.
2026-04-23 | GSE290143 | GEO
Project description:We profiled the zebrafish thymus by single-cell RNA sequencing to investigate the heterogeneity of zebrafish thymic epithelial cells and determine whether similar mimetic cell populations to those found in mice and humans might also exist in the zebrafish.
2024-12-14 | GSE259418 | GEO
Project description:Thymic alveolar type II epithelial mimetic cells revealed by Runx1-deficiency [CUT&Run]
| PRJNA1226264 | ENA
Project description:Thymic alveolar type II epithelial mimetic cells revealed by Runx1-deficiency [scRNA-seq]
| PRJNA1226263 | ENA
Project description:The generation of self-tolerant repertoires of T cells depends on the expression of peripheral self antigens in the thymic epithelium, and the presence of small populations of cells mimicking the diverse phenotypes of peripheral tissues. Whereas the molecular underpinnings of self-antigen expression have been extensively studied, the developmental origins and differentiation pathways of thymic mimetic cells remain to be identified. Moreover, the histological identification of myoid and other peripheral cell types as components of the thymic microenvironment of many vertebrate species raises questions as to the evolutionary origin of this unique tolerance mechanism. Here, we show that during mouse development, mimetic cells appear in the microenvironment in two successive waves. Cells exhibiting transcriptional signatures characteristic of muscle, ionocyte, goblet and ciliated cells emerge before birth, whereas others, for instance those mimicking enterohepatic cells and skin keratinocytes appear postnatally. These two groups also respond differently to modulations of TEC progenitor pools caused by deletions of Foxn1 and Ascl1, expression of a hypomorphic Foxn1 transcription factor, and overexpression of Bmp4 and Fgf7 signalling molecules. Differences in mimetic cell populations were also observed in thymic microenvironments reconstructed by replacement of mouse Foxn1 with evolutionarily ancient Foxn1/4 gene family members, including the Foxn4 gene of the cephalochordate amphioxus, and the Foxn4 and Foxn1 genes of a cartilaginous fish. Whereas some cell types, such as ciliated cells, develop in the thymus in the absence of Foxn1, mimetic cells appearing postnatally, such as enterohepatic cells, require the activity of the vertebrate-specific transcription factor Foxn1. The thymus of cartilaginous fishes and the thymoid of lampreys, a representative of jawless vertebrates that exhibit an alternative adaptive immune system, also harbour cells expressing genes encoding peripheral tissue components, such as the liver-specific protein transthyretin. Our findings suggest an evolutionary model of successive changes of thymic epithelial genetic networks enabling the coordinated contribution of peripheral antigen expression and mimetic cell formation to achieve central tolerance for vertebrate-specific innovations of certain tissues, such as the liver.
2025-04-15 | GSE272064 | GEO
Project description:The generation of self-tolerant repertoires of T cells depends on the expression of peripheral self antigens in the thymic epithelium, and the presence of small populations of cells mimicking the diverse phenotypes of peripheral tissues. Whereas the molecular underpinnings of self-antigen expression have been extensively studied, the developmental origins and differentiation pathways of thymic mimetic cells remain to be identified. Moreover, the histological identification of myoid and other peripheral cell types as components of the thymic microenvironment of many vertebrate species raises questions as to the evolutionary origin of this unique tolerance mechanism. Here, we show that during mouse development, mimetic cells appear in the microenvironment in two successive waves. Cells exhibiting transcriptional signatures characteristic of muscle, ionocyte, goblet and ciliated cells emerge before birth, whereas others, for instance those mimicking enterohepatic cells and skin keratinocytes appear postnatally. These two groups also respond differently to modulations of TEC progenitor pools caused by deletions of Foxn1 and Ascl1, expression of a hypomorphic Foxn1 transcription factor, and overexpression of Bmp4 and Fgf7 signalling molecules. Differences in mimetic cell populations were also observed in thymic microenvironments reconstructed by replacement of mouse Foxn1 with evolutionarily ancient Foxn1/4 gene family members, including the Foxn4 gene of the cephalochordate amphioxus, and the Foxn4 and Foxn1 genes of a cartilaginous fish. Whereas some cell types, such as ciliated cells, develop in the thymus in the absence of Foxn1, mimetic cells appearing postnatally, such as enterohepatic cells, require the activity of the vertebrate-specific transcription factor Foxn1. The thymus of cartilaginous fishes and the thymoid of lampreys, a representative of jawless vertebrates that exhibit an alternative adaptive immune system, also harbour cells expressing genes encoding peripheral tissue components, such as the liver-specific protein transthyretin. Our findings suggest an evolutionary model of successive changes of thymic epithelial genetic networks enabling the coordinated contribution of peripheral antigen expression and mimetic cell formation to achieve central tolerance for vertebrate-specific innovations of certain tissues, such as the liver.
2025-04-15 | GSE272063 | GEO
Project description:The generation of self-tolerant repertoires of T cells depends on the expression of peripheral self antigens in the thymic epithelium, and the presence of small populations of cells mimicking the diverse phenotypes of peripheral tissues. Whereas the molecular underpinnings of self-antigen expression have been extensively studied, the developmental origins and differentiation pathways of thymic mimetic cells remain to be identified. Moreover, the histological identification of myoid and other peripheral cell types as components of the thymic microenvironment of many vertebrate species raises questions as to the evolutionary origin of this unique tolerance mechanism. Here, we show that during mouse development, mimetic cells appear in the microenvironment in two successive waves. Cells exhibiting transcriptional signatures characteristic of muscle, ionocyte, goblet and ciliated cells emerge before birth, whereas others, for instance those mimicking enterohepatic cells and skin keratinocytes appear postnatally. These two groups also respond differently to modulations of TEC progenitor pools caused by deletions of Foxn1 and Ascl1, expression of a hypomorphic Foxn1 transcription factor, and overexpression of Bmp4 and Fgf7 signalling molecules. Differences in mimetic cell populations were also observed in thymic microenvironments reconstructed by replacement of mouse Foxn1 with evolutionarily ancient Foxn1/4 gene family members, including the Foxn4 gene of the cephalochordate amphioxus, and the Foxn4 and Foxn1 genes of a cartilaginous fish. Whereas some cell types, such as ciliated cells, develop in the thymus in the absence of Foxn1, mimetic cells appearing postnatally, such as enterohepatic cells, require the activity of the vertebrate-specific transcription factor Foxn1. The thymus of cartilaginous fishes and the thymoid of lampreys, a representative of jawless vertebrates that exhibit an alternative adaptive immune system, also harbour cells expressing genes encoding peripheral tissue components, such as the liver-specific protein transthyretin. Our findings suggest an evolutionary model of successive changes of thymic epithelial genetic networks enabling the coordinated contribution of peripheral antigen expression and mimetic cell formation to achieve central tolerance for vertebrate-specific innovations of certain tissues, such as the liver.
2025-04-15 | GSE272144 | GEO
Project description:The generation of self-tolerant repertoires of T cells depends on the expression of peripheral self antigens in the thymic epithelium, and the presence of small populations of cells mimicking the diverse phenotypes of peripheral tissues. Whereas the molecular underpinnings of self-antigen expression have been extensively studied, the developmental origins and differentiation pathways of thymic mimetic cells remain to be identified. Moreover, the histological identification of myoid and other peripheral cell types as components of the thymic microenvironment of many vertebrate species raises questions as to the evolutionary origin of this unique tolerance mechanism. Here, we show that during mouse development, mimetic cells appear in the microenvironment in two successive waves. Cells exhibiting transcriptional signatures characteristic of muscle, ionocyte, goblet and ciliated cells emerge before birth, whereas others, for instance those mimicking enterohepatic cells and skin keratinocytes appear postnatally. These two groups also respond differently to modulations of TEC progenitor pools caused by deletions of Foxn1 and Ascl1, expression of a hypomorphic Foxn1 transcription factor, and overexpression of Bmp4 and Fgf7 signalling molecules. Differences in mimetic cell populations were also observed in thymic microenvironments reconstructed by replacement of mouse Foxn1 with evolutionarily ancient Foxn1/4 gene family members, including the Foxn4 gene of the cephalochordate amphioxus, and the Foxn4 and Foxn1 genes of a cartilaginous fish. Whereas some cell types, such as ciliated cells, develop in the thymus in the absence of Foxn1, mimetic cells appearing postnatally, such as enterohepatic cells, require the activity of the vertebrate-specific transcription factor Foxn1. The thymus of cartilaginous fishes and the thymoid of lampreys, a representative of jawless vertebrates that exhibit an alternative adaptive immune system, also harbour cells expressing genes encoding peripheral tissue components, such as the liver-specific protein transthyretin. Our findings suggest an evolutionary model of successive changes of thymic epithelial genetic networks enabling the coordinated contribution of peripheral antigen expression and mimetic cell formation to achieve central tolerance for vertebrate-specific innovations of certain tissues, such as the liver.
2025-04-15 | GSE288957 | GEO
Project description:Fezf2 has been implicated in shaping tissue-restricted antigen (TRA) expression and as an “Aire-like” factor in the thymus. Here we demonstrate loss of Fezf2 results primarily in a developmental block in mTEC development with pronounced expansion of Ccl21a-expressing mTECs at the expense of thymic tuft cells and most Aire-high and recently described post-Aire “mimetic” populations. While loss of either Aire or Fezf2 leads to a loss of post-Aire mimetic subtypes, their transcriptional programs are distinct; whereas Aire positively regulates the expression of thousands of genome-wide targets, Fezf2 orchestrates a restricted transcriptional program balanced between induction and repression that largely impacts TEC development. Strikingly, most Fezf2-repressed genes map to Ccl21a-expressing mTECs, suggesting Fezf2 maintains a cellular state conducive to the development of Aire-expressing mTECs and downstream access to terminally differentiated mimetic programs. At least some mimetic cell programs appear to have functions beyond simply serving as antigen reservoirs; thymic microfold cells (M cells) organize the medullary B cell niche in a Ccr6-dependent manner and promote IgA class-switching, analogous to Peyer’s Patches. In Aire and Fezf2 KO mice, where development of thymic M cells is impaired, B cell class-switching is similarly disrupted. Therefore, our data reveal Fezf2 as a gatekeeper of mTEC terminal development which cooperates with Aire to allow the full program of medullary epithelial diversity, supporting unexpected layers of mimetic cell function that impact thymic homeostasis beyond antigen diversity.
2025-12-30 | GSE226493 | GEO
Project description:Methylation microarray data (Illumina 850K) of 52 thymic epithelial tumors. 13 patients with thymoma A and B, 32 thymic carcinoma (TC) and 7 neuroendocrine tumors of the thymus (NET).
| EGAD00010002355 | EGA