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SRP059777
Mus musculus
8 Downloadable Samples
Illumina HiSeq 2500
Description
To study the development and function of “natural-arising” T regulatory (nTreg) cells, we developed a novel nTreg model on pure nonobese diabetic background using epigenetic reprogramming via somatic cell nuclear transfer. On RAG1-deficient background, we found that monoclonal FoxP3+ CD4+ Treg cells developed in the thymus in the absence of other T cells. Adoptive transfer experiments revealed that the thymic niche is not a limiting factor in nTreg development. In addition, we showed that the T-cell receptor (TCR) ß-chain of our nTreg model was not only sufficient to bias T-cell development toward the CD4 lineage, but we also demonstrated that this TCR ß-chain was able to provide stronger TCR signals. This TCR-ß–driven mechanism would thus unify former per se contradicting hypotheses of TCR-dependent and -independent nTreg development. Strikingly, peripheral FoxP3- CD4+ T cells expressing the same TCR as this somatic cell nuclear transfer nTreg model had a reduced capability to differentiate into Th1 cells but were poised to differentiate better into induced nTreg cells, both in vitro and in vivo, representing a novel peripheral precursor subset of nTreg cells to which we refer to as pre-nTreg cells. Overall design: We performed RNA-Seq analysis to determine the transcriptional differences between monoclonal FoxP3GFP-positive and -negative CD4+ T cells from NOD.TCRab.FoxP3GFP.Rag-/- and compared it with polyclonal FoxP3GFP-positive and -negative CD4+ T cells from NOD.FoxP3GFP mice
Publication Title
Nuclear transfer nTreg model reveals fate-determining TCR-β and novel peripheral nTreg precursors.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- NextSeq 500
Description
Granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs) produce monocytes during homeostasis and in response to increased demand during infection. Both progenitor populations are thought to derive from common myeloid progenitors (CMPs), and a hierarchical relationship (CMP-GMP-MDP-monocyte) is presumed to underlie monocyte differentiation. Here, however, we demonstrate that mouse MDPs arose from CMPs independently of GMPs, and that GMPs and MDPs produced monocytes via similar, but distinct, monocyte-committed progenitors. GMPs and MDPs yielded classical (Ly6Chi) monocytes with gene expression signatures that were defined by their origins and impacted their function. GMPs produced a subset of “neutrophil-like” monocytes, whereas MDPs gave rise to a subset of monocytes that yielded monocyte-derived dendritic cells. GMPs and MDPs were also independently mobilized to produce specific combinations of myeloid cell types following the injection of microbial components. Thus, the balance of GMP and MDP differentiation shapes the myeloid cell repertoire during homeostasis and following infection. Overall design: RNA-seq of myeloid progenitors and Ly6Chi monocytes from mouse bone marrow. 4 progenitor fractions (GMPs, MDPs, GPs and a mixed fraction of MPs + cMoPs) were isolated from the pooled bone marrow of 20 mice. GMPs and MDPs were also cultured in vitro and the monocyte-committed progenitors and Ly6Chi monocytes they produced were also harvested. RNA was extracted from the 4 ex vivo progenitor fractions, and the 4 populations derived in vitro (GMP-derived monocyte progenitors = MP; MDP-derived monocyte progenitors = cMoP; GMP-derived Ly6Chi monocytes = G-mono; MDP-derived Ly6Chi monocytes = M-mono). The whole process was repeated using 20 additional mice to obtain a replicate set of samples.
Publication Title
Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 4000
Description
Purpose: We designed this study to evaluate the feasibility of using only one factor to respecify human induced pluripotent stem cells (iPSCs)-derived blood cells into long-term engraftable hematopoietic stem and progenitor cells (HSPCs). We also parallelly compared iPSC-derived HSPCs (iHSPCs) with primary HSPCs under the same induction and transplantation condition in order to examine the functional equivalency between iHSPCs and bona fide HSPCs. Methods: In vitro derived human iPSC-HSPCs are induced with or without (w/o) doxycycline for the expression of MLL-AF4. In vivo derived bone marrow cells are harvested and FACS-sorted for human populations from primary transplants over nine to sixteen weeks after transplantation. Either iPSC-HSPCs or primary HSPCs, both of which are induced by MLL-AF4, is used for the transplantation experiments. iPSCs are either derived from peripheral blood mobilized CD34+ HSPCs (CD34-iPSC) or mononuclear cells (MN-iPSCs). Normal human CD34+ HSPCs and mononuclear cells are set as control groups. Results: MLL-AF4 can impart HSC and lymphoid potential to iPSC-derived blood cells in vitro, and induction of MLL-AF4 leads to the cellular identity transition from common myeloid progenitors to hematopoietic stem and progenitor cells. MLL-AF4 alone is sufficient to realize the potent engraftment of induced HSPCs (iHSPCs) from iPSCs, and multilineage and long-term hematopoiesis could be observed. Primary HSPCs with the induction of MLL-AF4 could gain significantly enhanced engraftability. During the long-term engraftment period, leukemic mutations with a bias to B-cell leukemia could be found in the iHSPCs and their derivatives. By contrast, MLL-AF4 induced primary HSPCs maintain the normal hematopoiesis without leukemic transformation. Conclusions: Our study has demonstrated for the first time, to our knowledge, that the pluripotency-dependent conversion of somatic cells to long-term engraftable HSPCs can be achieved by using a single factor in a non-integrative way. This study also suggests that iPSC-derived HSPCs are more prone to leukemic mutations during the long-term engraftment period, which provides a necessary caveat of using them in the actual therapies. Overall design: Human mRNA profiles of either in vitro derived iPSC-HSPCs or engrafted NSG mice were generated by deep sequencing, in triplicate, using Illumina HiSeq 4000.
Publication Title
Respecifying human iPSC-derived blood cells into highly engraftable hematopoietic stem and progenitor cells with a single factor.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 94 Downloadable Samples
- Illumina HiSeq 2500
Description
Delineating key HSC regulators is of significant interest for informing the treatment of hematologic malignancy. While HSC activity is enhanced by overexpression of SKI, the transforming growth factor-beta (TGFß) signaling antagonist corepressor, its requirement in HSC is unknown. Here we reveal a profound defect in Ski-/- HSC fitness but not specification. Transcriptionally, Ski-/- HSC exhibited striking upregulation of TGFb superfamily signaling and splicing alterations. As these are both common aspects of myelodysplastic-syndrome (MDS) pathobiology with prognostic value, we investigated the role of SKI in MDS. A SKI-correlated gene signature defines a subset of low-risk MDS patients with active TGFß signaling and deregulated RNA splicing (e.g. CSF3R). The apparent paradox of Ski-/- HSC sharing molecular aspects of MDS with elevated SKI-mRNA is resolved by miR-21 targeting of SKI in MDS. We conclude that miR-21-mediated loss of SKI contributes to early stage MDS pathogenesis by activating TGFß signaling and alternative splicing while hindering HSC fitness. Overall design: Single cell RNA seq of transplanted fetal liver-derived hematopoietic stem cells
Publication Title
<i>SKI</i> controls MDS-associated chronic TGF-β signaling, aberrant splicing, and stem cell fitness.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- NextSeq 500
Description
We performed a single-cell transcriptome analysis of double-negative developing thymocytes from the DN2, DN3 and DN4 populations Overall design: Double-negative developing thymocytes from the DN2, DN3 and DN4 populations were sorted from six WT mice and used for single cell RNA Seq (10x genomics platform)
Publication Title
The transcription factor Duxbl mediates elimination of pre-T cells that fail β-selection.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- NextSeq 500
Description
We performed a transcriptome comparison of double-negative developing thymocytes from the DN3-4 population, from mice overexpressing the transcription factor Duxbl and wild type mice Overall design: Double-negative developing thymocytes from both WT and Duxbl[ind]xpTa[Cre] mice were gated for CD4-, CD8-, CD3-, B220-, CD25int, CD44low and CD117low expression, which define the DN3-4 stage of thymocyte development. The experiment was performed in four replicates, giving a total of 8 samples.
Publication Title
The transcription factor Duxbl mediates elimination of pre-T cells that fail β-selection.
Sample Metadata Fields
Sex, Cell line, Subject
View Samples- Homo sapiens
- 31 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A global DNA methylation and gene expression analysis of early human B-cell development reveals a demethylation signature and transcription factor network.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A global DNA methylation and gene expression analysis of early human B-cell development reveals a demethylation signature and transcription factor network. Nucleic Acids Res. 2012 Dec;40(22):11339-51.
Publication Title
A global DNA methylation and gene expression analysis of early human B-cell development reveals a demethylation signature and transcription factor network.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
In this study we used Illumina Microarray to compare the induction of immune related genes following enteric virus infection. Results show that infection of T3D mammalian reovirus from the basolateral side lead to a higher induction of all genes compared to apical infection.
Publication Title
Asymmetric distribution of TLR3 leads to a polarized immune response in human intestinal epithelial cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 81 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st), Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482), Illumina HiSeq 2000
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Epigenetic remodeling in B-cell acute lymphoblastic leukemia occurs in two tracks and employs embryonic stem cell-like signatures.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples