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Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE129856 | GEO | 2020/05/26

REPOSITORIES: GEO

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Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development [BCL11B_coculture]

Project description:Notch-dependent BCL11B induction converts thymus seeding precursor cells into committed T cell progenitors that subsequently differentiate into T cells bearing either the γδ or αβ T cell receptor. In human, strong Notch activation favors γδ T cell development at the expense of αβ-lineage differentiation, but the underlying molecular mechanism has remained unclear. Therefore, we performed paired mRNA and miRNA profiling across 11 stages of human T cell development, including developing γδ T cells. We identify the miR-17-92 cluster as a direct Notch target and show that miR-17 promotes human TCRγδ T cell development by targeting BCL11B, a gene required for αβ but not for γδ T cell development. Thus, following its role as a licensing factor to induce BCL11B expression in early T cell precursors, Notch activation limits BCL11B expression through miR-17 until thymocytes have passed the β-selection checkpoint when Notch activation is turned off. Hereby Notch prevents premature BCL11B upregulation that is required for αβ-lineage differentiation and this results in preferential γδ-lineage differentiation. Our work unravels a dual role for Notch in controlling BCL11B expression during intrathymic differentiation and provides a unique resource for understanding the mRNA/miRNA interactions that control human T cell development. We used microarrays in order to profile gene expression in CD34+ thymocytes before culture and after 5 or 10 days culture on OP9 stromal cells expressing Notch ligands JAG1, JAG2, DLL1 or DLL4.

2020-05-26 | GSE129853 | GEO

Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development [miRNA BCL11B_coculture]

Project description:Notch-dependent BCL11B induction converts thymus seeding precursor cells into committed T cell progenitors that subsequently differentiate into T cells bearing either the γδ or αβ T cell receptor. In human, strong Notch activation favors γδ T cell development at the expense of αβ-lineage differentiation, but the underlying molecular mechanism has remained unclear. Therefore, we performed paired mRNA and miRNA profiling across 11 stages of human T cell development, including developing γδ T cells. We identify the miR-17-92 cluster as a direct Notch target and show that miR-17 promotes human TCRγδ T cell development by targeting BCL11B, a gene required for αβ but not for γδ T cell development. Thus, following its role as a licensing factor to induce BCL11B expression in early T cell precursors, Notch activation limits BCL11B expression through miR-17 until thymocytes have passed the β-selection checkpoint when Notch activation is turned off. Hereby Notch prevents premature BCL11B upregulation that is required for αβ-lineage differentiation and this results in preferential γδ-lineage differentiation. Our work unravels a dual role for Notch in controlling BCL11B expression during intrathymic differentiation and provides a unique resource for understanding the mRNA/miRNA interactions that control human T cell development. The expression of 756 miRNAs was determined using the Taqman stem-loop RT-qPCR method as previously described (Mets E. Leukemia. 2015, Mavrakis KJ. Nat Genet. 2011).

2020-05-26 | GSE129855 | GEO

Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development [BCL11B_ex vivo]

Project description:Notch-dependent BCL11B induction converts thymus seeding precursor cells into committed T cell progenitors that subsequently differentiate into T cells bearing either the γδ or αβ T cell receptor. In human, strong Notch activation favors γδ T cell development at the expense of αβ-lineage differentiation, but the underlying molecular mechanism has remained unclear. Therefore, we performed paired mRNA and miRNA profiling across 11 stages of human T cell development, including developing γδ T cells. We identify the miR-17-92 cluster as a direct Notch target and show that miR-17 promotes human TCRγδ T cell development by targeting BCL11B, a gene required for αβ but not for γδ T cell development. Thus, following its role as a licensing factor to induce BCL11B expression in early T cell precursors, Notch activation limits BCL11B expression through miR-17 until thymocytes have passed the β-selection checkpoint when Notch activation is turned off. Hereby Notch prevents premature BCL11B upregulation that is required for αβ-lineage differentiation and this results in preferential γδ-lineage differentiation. Our work unravels a dual role for Notch in controlling BCL11B expression during intrathymic differentiation and provides a unique resource for understanding the mRNA/miRNA interactions that control human T cell development. We used microarrays in order to profile the gene expression in 11 ex vivo T cell subsets, isolated from human thymus. Cord blood CD34+Lin- HPCs were used as a reference subset for extrathymic HPCs.

2020-05-26 | GSE129852 | GEO

Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development [miRNA BCL11B_ex vivo]

Project description:Notch-dependent BCL11B induction converts thymus seeding precursor cells into committed T cell progenitors that subsequently differentiate into T cells bearing either the γδ or αβ T cell receptor. In human, strong Notch activation favors γδ T cell development at the expense of αβ-lineage differentiation, but the underlying molecular mechanism has remained unclear. Therefore, we performed paired mRNA and miRNA profiling across 11 stages of human T cell development, including developing γδ T cells. We identify the miR-17-92 cluster as a direct Notch target and show that miR-17 promotes human TCRγδ T cell development by targeting BCL11B, a gene required for αβ but not for γδ T cell development. Thus, following its role as a licensing factor to induce BCL11B expression in early T cell precursors, Notch activation limits BCL11B expression through miR-17 until thymocytes have passed the β-selection checkpoint when Notch activation is turned off. Hereby Notch prevents premature BCL11B upregulation that is required for αβ-lineage differentiation and this results in preferential γδ-lineage differentiation. Our work unravels a dual role for Notch in controlling BCL11B expression during intrathymic differentiation and provides a unique resource for understanding the mRNA/miRNA interactions that control human T cell development. The expression of 756 miRNAs and 3 small RNA controls was determined using the Taqman stem-loop RT-qPCR method as previously described (Mets E. Leukemia. 2015, Mavrakis KJ. Nat Genet. 2011).

2020-05-26 | GSE129854 | GEO

Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development

Project description:Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development

| PRJNA533059 | ENA

Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development [BCL11B_coculture]

Project description:Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development [BCL11B_coculture]

| PRJNA533188 | ENA

Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development [BCL11B_ex vivo]

Project description:Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development [BCL11B_ex vivo]

| PRJNA533187 | ENA

Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development [miRNA BCL11B_coculture]

Project description:Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development [miRNA BCL11B_coculture]

| PRJNA533190 | ENA

Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development [miRNA BCL11B_ex vivo]

Project description:Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development [miRNA BCL11B_ex vivo]

| PRJNA533189 | ENA

Transcriptional regulation of human αβ and γδ T cell development is driven by distinct and temporary-restricted epigenetic mechanism

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-07-29 | GSE151081 | GEO

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