Identification of fibroblast progenitors in the developing thymus
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB50163 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR8048470.fastq.gz | Fastqsanger.gz | |||
| ERR8049260.fastq.gz | Fastqsanger.gz | |||
| ERR8049092.fastq.gz | Fastqsanger.gz | |||
| ERR8049262.fastq.gz | Fastqsanger.gz | |||
| ERR8049572.fastq.gz | Fastqsanger.gz |
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Project description:The thymus stroma constitutes a fundamental microenvironment for T-cell generation. Despite the chief contribution of thymic epithelial cells, recent studies emphasize the regulatory role of mesenchymal cells in thymic function. Mesenchymal progenitors are suggested to exist in the postnatal thymus; nonetheless, an understanding of their nature and the mechanism controlling their homeostasis in vivo remains elusive. We resolved two new thymic fibroblast subsets with distinct developmental features. Whereas CD140αβ+GP38+SCA-1- cells prevailed in the embryonic thymus and declined thereafter, CD140αβ+GP38+SCA-1+ cells emerged in the late embryonic period and predominated in postnatal life. The fibroblastic-associated transcriptional programme was upregulated in CD140αβ+GP38+SCA-1+ cells, suggesting that they represent a mature subset. Lineage analysis showed that CD140αβ+GP38+SCA-1+ maintained their phenotype in thymic organoids. Strikingly, CD140αβ+GP38+SCA-1- generated CD140αβ+GP38+SCA-1+, inferring that this subset harboured progenitor cell activity. Moreover, the abundance of CD140αβ+GP38+SCA-1+ fibroblasts was gradually reduced in Rag2-/- and Rag2-/-Il2rg-/- thymi, indicating that fibroblast maturation depends on thymic crosstalk. Our findings identify CD140αβ+GP38+SCA-1- as a source of fibroblast progenitors and define SCA-1 as a marker for developmental stages of thymic fibroblast differentiation.
| S-EPMC9188757 | biostudies-literature
Project description:Since the first description of the involvement of Notch signaling in homeostasis especially of T cells, there is great effort in research to find new target genes of Notch that are involved in T cell development in the thymus. We developed a stroma cell free system that is able to induce T cell development in vitro called the plastic thymus. Having this new tool we decided to use the gene expression technique to get an expanded and more global picture of the changes in gene expression in T cell progenitor induced by Notch signaling via DLL4-Fc. We used microarrays to detail the global programme of gene expression in developing T-cell progenitors induced by Notch signaling. T cell progenitors generated in the plastic thymus, defined as CD93 lo, c-Kit+ cells were sorted on day 5, RNA was isolated and gene expression was analyzed using Affymetrix GeneChip Mouse Gene 1.0 ST Array. PC5B7 cultured with IL7 and SCF were stimulated with 2 μg/ml plate bound DLL4-Fc and compared to cells cultured without the Notch ligand.
2013-05-31 | E-GEOD-46191 | biostudies-arrayexpress
Project description:Gene expression analysis of early thymic progenitors and thymus seeding progenitors Eight distinct populations were analysed, each with between 2 and 6 biological replicates.
2012-02-19 | E-GEOD-29382 | biostudies-arrayexpress
Project description:Gene expression analysis of early thymic progenitors and thymus seeding progenitors
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Project description:Since the first description of the involvement of Notch signaling in homeostasis especially of T cells, there is great effort in research to find new target genes of Notch that are involved in T cell development in the thymus. We developed a stroma cell free system that is able to induce T cell development in vitro called the plastic thymus. Having this new tool we decided to use the gene expression technique to get an expanded and more global picture of the changes in gene expression in T cell progenitor induced by Notch signaling via DLL4-Fc. We used microarrays to detail the global programme of gene expression in developing T-cell progenitors induced by Notch signaling.
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Project description:Human T lymphogenesis includes emergence, migration and thymus-seeding of T lymphoid precursor, followed by T-lymphocytes commitment in thymus, which are largely unknown. Here, we perform single-cell RNA sequencing using cells isolated from human hemogenic/hematopoietic sites such as aorto-gonad-mesonephros (AGM), liver, and thymic primordia spanning embryonic and fetal stages. The transcriptional atlas of thymic primordia illustrates the cellular trajectory of early T-lymphocyte development. Further, thymic seeding progenitors in liver and unique T lymphoid progenitors in AGM at CS14, are first unveiled. We also reveal the stepwise-specification of thymic epithelial cells，and the potential cell-cell interactions between T-lymphocyte progenitors and stromal cells during thymus organogenesis. Our data provide new insights into T lymphogenesis, which prospectively directs the efficient regeneration of T- lymphocytes from pluripotent stem cells
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Project description:It is generally believed that cerebellar granule neurons originate exclusively from granule neuron precursors (GNPs) in the external germinal layer (EGL). Here we identify a rare population of neuronal progenitors in the developing cerebellum that expresses Nestin. Although Nestin is widely considered a marker for multipotent stem cells, these Nestin-expressing progenitors (NEPs) are committed to the granule neuron lineage. Unlike conventional GNPs, which reside in the outer EGL and proliferate extensively, NEPs reside in the deep part of the EGL and are quiescent. Expression profiling reveals that NEPs are distinct from GNPs, and in particular, express markedly reduced levels of genes associated with DNA repair. Consistent with this, upon aberrant activation of Sonic hedgehog (Shh) signaling, NEPs exhibit more severe genomic instability and give rise to tumors more efficiently than GNPs. These studies identify a novel progenitor for cerebellar granule neurons and a novel cell of origin for medulloblastoma.
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2025-05-27 | MSV000097998 | MassIVE