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Integrated scRNA-Seq Identifies Human Postnatal Thymus Seeding Progenitors and Regulatory Dynamics of Differentiating Immature Thymocytes

ABSTRACT: Integrated scRNA-Seq Identifies Human Postnatal Thymus Seeding Progenitors and Regulatory Dynamics of Differentiating Immature Thymocytes

PROVIDER: PRJNA605194 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11039255.fastq.gz	Fastqsanger.gz
	SRR11039256.fastq.gz	Fastqsanger.gz
	SRR11039257.fastq.gz	Fastqsanger.gz
	SRR11039258.fastq.gz	Fastqsanger.gz
	SRR11039259.fastq.gz	Fastqsanger.gz

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Integrated scRNA-Seq Identifies Human Postnatal Thymus Seeding Progenitors and Regulatory Dynamics of Differentiating Immature Thymocytes

Project description:During postnatal life, thymopoiesis depends on the continuous colonization of the thymus by bone marrow-derived hematopoietic progenitors that migrate through the bloodstream. The current understanding of the nature of thymic immigrants is largely based on data from pre-clinical models. Here, we employed single-cell RNA sequencing (scRNA-seq) to examine the immature postnatal thymocyte population in humans. Integration of bone marrow and peripheral blood precursor datasets identified two putative thymus seeding precursors that varied in expression of CD7; CD10; and the homing receptors CCR7, CCR9, and ITGB7. Whereas both precursors supported T cell development, only one contributed to intrathymic dendritic cell (DC) differentiation, predominantly of plasmacytoid dendritic cells. Trajectory inference delineated the transcriptional dynamics underlying early human T lineage development, enabling prediction of transcription factor (TF) modules that drive stage-specific steps of human T cell development. This comprehensive dataset defines the expression signature of immature human thymocytes and provides a resource for the further study of human thymopoiesis.

2020-04-17 | GSE144870 | GEO

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.

2012-02-19 | E-GEOD-29382 | biostudies-arrayexpress

Characterisation of early thymic progenitors and thymus seeding progenitors

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

2012-02-19 | GSE29382 | GEO

Single-cell immune profiling reveals thymus-seeding populations, T cell commitment, and multi-lineage development in the human thymus

Project description:Development of T lymphocytes in the thymus has been widely studied in mice, but our insights into human T cell development are scarce. Using a combination of single-cell techniques and functional assays, we report deep immune profiling of human T cell development, with a focus on the initial development stages of pre-lineage commitment. We identified three thymus-seeding progenitor populations that also have a counterpart in the bone marrow. We found that the human thymus physiologically supports development of monocytes, DCs, NK cells, and limited development of B lymphocytes. These insights are important to monitor and guide regenerative therapies after hematopoietic stem cell transplantation.

2022-08-01 | GSE195812 | GEO

Identification of the molecular targets of microRNA-181d in murine thymocytes.

Project description:T cell-specific transgenic expression of microRNA-181d reduced number of immature CD4+CD8+ thymocytes. Microarray analysis was performed to reveal differentially expressed genes between the wild type and microRNA-181d transgenic thymocytes. Whole thymus tissues were isolated from the wild type (C57BL/6) and microRNA-181d transgenic mice (Tg-38 line), followed by total RNA isolation.

2014-01-21 | E-GEOD-51778 | biostudies-arrayexpress

Gene expression comparison of microRNA-181d Transgenic and microRNA-181d Knock-in thymocytes

Project description:T cell-specific over-expression of microRNA-181d reduced number of immature CD4+CD8+ thymocytes. Whole thymus tissues were isolated from the miR-181d transgenic (Tg-8) and miR-181d knockin (KI) mice, followed by total RNA isolation.

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Real-time quantitative PCR analysis of mouse immature CD4SP thymocytes

Project description:RNA was isolated with the RNeasy kit (Qiagen) from electronically sorted immature CD4SP thymocytes. RNA was reverse transcribed into cDNA by oligo(dT) priming with the QuantiTect Reverse transcription kit (Qiagen). The expression of 84 key genes involved in apoptosis, or programmed cell death was performed with mouse apoptosis RT2ProfilerTM PCR array system (PAMM-012 E; SABiosciences). PCR Array data were analyzed by the Ct data analysis method. qPCR gene expression profiling. CD4SP thymocytes from WT and Ik7Tg mice were used.

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mRNA expression of Qa2+ and Qa2- CD4+ thymocytes isolated from WT and miR-142-/- mice

Project description:Developing CD4+ T-cells in the thymus mature from CD69+Qa2- cells to CD69-Qa2+ T-cells. This maturation is accombanied by increased expression of CD62L and S1PR1 in Qa2+ cells, which allows mature T-cells to emigrate from the thymus to the periphery. However, miR-142-/- mice are characterized by an altered thymocytes homeostasis, characterized by reduced CD62L protein levels on their cell surface. To characterize the underlying molecular mechanisms, which lead to reduced CD62L expression in miR-142-/- CD4+ thymocytes, we investigated the mRNA levels in immature Qa2- as well as mature Qa2+ thymocytes isolated ex vivo from WT and miR-142 deficient Bl6 mice.

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Project description:Single cell suspensions of total thymocytes were obtained from Pten enhancer (PE) wild-type or knockout mice. This single-cell suspension was enriched in CD4-CD3- immature thymocyte progenitor cells. CD4-CD3- enriched thymocytes were then mixed 1:1 with single-cell suspensions from total unenriched thymocytes and subsequntly loaded in a 10x Chromium instrument for single-cell RNAseq analyses. Our results revealed Pten levels are signifcantly decreased in CD4-CD8- double negative (DN) thymocytes, CD8+ intermediate single positive (ISP) thymocytes and CD4+CD8+ double positive (DP) thymocytes in PE knockout mice, compared to PE wild-type mice.

2020-12-17 | GSE156070 | GEO

miRNA expression in PTEN-deficient premalignant DP thymocytes

Project description:T cell-specific deletion of PTEN induces premalignancy in CD4+ CD8+ (DP) immature T cells in the thymus, which progresses to the development of mature CD4+ T cell lymphomas in the lymph nodes and spleen. As part of a screen to identify factors that inhibit progression to malignancy, we compared miRNA expression in premalignant PTEN-deficient DP thymocytes versus wild-type controls.

2014-04-12 | GSE56759 | GEO

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