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SRP137222
Mus musculus
12 Downloadable Samples
Illumina HiSeq 2000
Description
Hereditary sensory and autonomic neuropathy type I (HSAN-I) is neurological disorder characterized by distal sensory neuron dysfunction, frequent infections, and ulcerative mutilations. It remains unknown if HSAN-I directly dampens protective immunity. Here we report that HSAN-I-causing mutations of serine palmitoyltransferase long chain base subunit 2 (SPTLC2) affect human T cell responses. T cell antigenic stimulation and inflammation induce SPTLC2 expression. Murine T cell-specific ablation of Sptlc2 fundamentally impairs antiviral T cell survival and effector function. Mechanistically, SPTLC2-deficiency reduces sphingolipid biosynthetic flux and causes a prolonged activation of the mechanistic target of rapamycin complex 1 (mTORC1), endoplasmic reticulum (ER) stress and CD8+ T cell death. Antiviral CD8+ T cell responses are restored by supplementing sphingolipids and pharmacologically inhibiting ER stress-induced cell death. Our study reveals that SPTLC2 underpins protective adaptive immunity by translating extracellular stimuli into intracellular anabolic signals and reducing cellular stress to maintain metabolic reprogramming sustainability Overall design: Triplicates of each group were used for RNA-seq. Four groups were studied: Wild-type and SPTLC2-deficient CD8+ T cells, harvested from either naïve mice (D0) or mice infected with LCMV Armstrong 8 days earlier (D8).
Publication Title
Loss of Neurological Disease HSAN-I-Associated Gene SPTLC2 Impairs CD8<sup>+</sup> T Cell Responses to Infection by Inhibiting T Cell Metabolic Fitness.
Alternate Accession IDs
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 60 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Injury of skeletal muscle is a common occurence affecting millions worldwide. Injuries usually are not major incisions into daily life, however, the underlying health varies e. g. due to obesity. Obesity is usually accompanied by excessive and dysfunctional lipid depots, chronic low-grade inflammation as well as several co-morbidities, which are able to impair the regeneration of skeletal muscle.
Publication Title
Comparison of Fatty Acid and Gene Profiles in Skeletal Muscle in Normal and Obese C57BL/6J Mice before and after Blunt Muscle Injury.
Alternate Accession IDs
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Human T-cell development is less well studied than its murine counterpart due to the lack of genetic tools and the difficulty of obtaining cells and tissues. However, recent technological advances allow identification of the transcriptional landscape of differentiating human thymocytes. Here we report the gene expression profiles of 11 immature, consecutive T-cell developmental stages. The changes in gene expression of cultured stem cells on OP9-DL1 match those of ex vivo isolated human thymocytes. These analyses led us to define evolutionary conserved gene signatures that represent pre- and post- T-cell commitment stages. We found that loss of CD44 marks T-cell commitment in early CD7+CD5+CD45dim cells, before the acquisition of CD1a surface expression. The CD44-CD1a- post-committed thymocytes have initiated in frame TCR rearrangements and have completely lost the capacity to develop into myeloid, B- and NK-cells, unlike uncommitted CD44+CD1a- thymocytes. Therefore, loss of CD44 represents a previously unrecognized stage that defines the earliest committed T-cell population in the human thymus.
Publication Title
Loss of CD44<sup>dim</sup> Expression from Early Progenitor Cells Marks T-Cell Lineage Commitment in the Human Thymus.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- IlluminaHiSeq2000
Description
We report molecular characterization of human brown and white adipocytes. We showed that PAZ6 and SW872 cells exhibit classical molecular and phenotypic markers of brown and white adipocytes, respectively. However, SGBS cells presented a versatile phenotype of adipocyte Overall design: Sequencing of three human adipocytes cell lines (SGBS, SW872 and PAZ6) in undifferentiated and differentiated stages.
Publication Title
Comprehensive molecular characterization of human adipocytes reveals a transient brown phenotype.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
In a screen for upregulated adipocyte genes in insulin resistant versus insulin sensitive subjects matched for BMI, we identified the type II transmembrane protein tenomodulin (TNMD), previously implicated in glucose tolerance in gene association studies. TNMD expression was greatly increased in human preadipocytes during differentiation, while silencing TNMD blocked adipogenic gene induction and adipogenesis.
Publication Title
Tenomodulin promotes human adipocyte differentiation and beneficial visceral adipose tissue expansion.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Expression profiling of progenitor cells from human supraclavicular and subcutaneous adipose tissue. Studies in animal models revealed that brown and white adipocytes derive from different progenitor cells. Molecular characteristics of these cells have not been investigated in detail in humans.
Publication Title
Comparative gene array analysis of progenitor cells from human paired deep neck and subcutaneous adipose tissue.
Alternate Accession IDs
Sample Metadata Fields
Sex, Age
View Samples