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Identification of fibroblast progenitors in the developing thymus

ABSTRACT: Identification of fibroblast progenitors in the developing thymus

PROVIDER: PRJEB50163 | ENA |

REPOSITORIES: ENA

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			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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Identification of fibroblast progenitors in the developing mouse thymus.

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.

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Gene expression data from T-cell progenitors developing in response to DLL4 stimulation in the plastic thymus

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 Î¼g/ml plate bound DLL4-Fc and compared to cells cultured without the Notch ligand.

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Characterisation of early thymic progenitors and thymus seeding progenitors

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.

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Characterisation of early thymic progenitors and thymus seeding progenitors

Project description:Gene expression analysis of early thymic progenitors and thymus seeding progenitors

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Gene expression data from T-cell progenitors developing in response to DLL4 stimulation in the plastic thymus

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Generation of thymus reconstituting T cell progenitors from genetically unmodified human pluripotent stem cells

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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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