Transplanting renal allografts represents the major curative treatment of chronic renal failure. Despite recent advances in immunosuppressive therapy, long-term survival of allografts remains a major clinical problem. Kidney function depends in part on transport proteins such as MRP2 (ABCC2) which facilitates renal secretion of amphiphilic exogenous and endogenous compounds. Inherited variants of genes not related to the immune system have been shown to modify the outcome after renal transplantation. We investigated whether ABCC2 gene variants in the donor kidney affect renal graft function.
Multidrug resistance-related protein 2 genotype of the donor affects kidney graft function.
Sex
View SamplesThe cortical area map is initially patterned by transcription factor (TF) gradients in the neocortical primordium, which define a protomap in the embryonic ventricular zone (VZ). However, mechanisms that propagate regional identity from VZ progenitors to cortical plate (CP) neurons are unknown. Here we show that the VZ, subventricular zone (SVZ), and CP contain distinct molecular maps of regional identity, reflecting different gene expression gradients in radial glia progenitors, intermediate progenitors, and projection neurons, respectively. The intermediate map in SVZ is modulated by Eomes (also known as Tbr2), a T-box TF. Eomes inactivation caused rostrocaudal shifts in SVZ and CP gene expression, with loss of corticospinal axons and gain of corticotectal projections. These findings suggest that cortical areas and connections are shaped by sequential maps of regional identity, propagated by the Pax6 Eomes Tbr1 TF cascade. In humans, PAX6, EOMES, and TBR1 have been linked to intellectual disability and autism.
The protomap is propagated to cortical plate neurons through an Eomes-dependent intermediate map.
Specimen part
View SamplesAreas and layers of the cerebral cortex are specified by genetic programs that are initiated in progenitor cells and then, implemented in postmitotic neurons. Here, we report that Tbr1, a transcription factor expressed in postmitotic projection neurons, exerts positive and negative control over both regional (areal) and laminar identity. Tbr1 null mice exhibited profound defects of frontal cortex and layer 6 differentiation, as indicated by down-regulation of gene-expression markers such as Bcl6 and Cdh9. Conversely, genes that implement caudal cortex and layer 5 identity, such as Bhlhb5 and Fezf2, were up-regulated in Tbr1 mutants. Tbr1 implements frontal identity in part by direct promoter binding and activation of Auts2, a frontal cortex gene implicated in autism. Tbr1 regulates laminar identity in part by downstream activation or maintenance of Sox5, an important transcription factor controlling neuronal migration and corticofugal axon projections. Similar to Sox5 mutants, Tbr1 mutants exhibit ectopic axon projections to the hypothalamus and cerebral peduncle. Together, our findings show that Tbr1 coordinately regulates regional and laminar identity of postmitotic cortical neurons.
Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex.
Specimen part
View SamplesTechnical advances have enabled the collection of genome and transcriptome data sets with single-cell resolution. However, single-cell characterization of the epigenome has remained challenging. Furthermore, because cells must be physically separated prior to biochemical processing, conventional single-cell preparatory methods scale linearly. We applied combinatorial cellular indexing to measure chromatin accessibility in thousands of single cells per assay, circumventing the need for compartmentalization of individual cells. We report chromatin accessibility profiles from over 15,000 single cells and use these data to cluster cells on the basis of chromatin accessibility landscapes. We identify modules of coordinately regulated chromatin accessibility at the level of single cells both between and within cell types, with a scalable method that may accelerate progress toward a human cell atlas. Overall design: 3 replicates from GM12878 and HL-60 cell lines collected for differential gene expression analysis.
Multiplex single cell profiling of chromatin accessibility by combinatorial cellular indexing.
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Effects of maternal obesity on Wharton's Jelly mesenchymal stromal cells.
Specimen part, Subject
View SamplesIn this study, we evaluated global Mtb-induced gene expression in airway immune cells obtained by bronchoalveolar lavage of individuals with latent tuberculosis infection (LTBI) and in Mtb-naïve control subjects
<i>Mycobacterium tuberculosis</i>-Induced Bronchoalveolar Lavage Gene Expression Signature in Latent Tuberculosis Infection Is Dominated by Pleiotropic Effects of CD4<sup>+</sup> T Cell-Dependent IFN-γ Production despite the Presence of Polyfunctional T Cells within the Airways.
Specimen part, Disease
View SamplesWe studied the influence of the oleic acid content of the diet on adipose tissue transcriptome.
Dietary energy source largely affects tissue fatty acid composition but has minor influence on gene transcription in Iberian pigs.
Sex, Specimen part, Treatment
View SamplesHere we describe sci-CAR, a combinatorial indexing strategy to jointly profile chromatin accessibility and mRNA in each of thousands of single cells. As a proof-of-concept, we apply sci-CAR to 4,825 cells comprising a time-series of dexamethasone treatment, as well as to 11,233 cells from the mouse kidney. Overall design: single cell RNA-seq and ATAC-seq co-profiling for HEK293T cells, NIH/3T3 cells, A549 cells across three treatment conditions (DEX 0 hour, 1 hour and 3 hour treatment), and wild type mouse kidney.
Joint profiling of chromatin accessibility and gene expression in thousands of single cells.
No sample metadata fields
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