Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid...

Plasmacytoid dendritic cells (pDCs) represent a rare innate immune subset uniquely endowed with the capacity to produce substantial amounts of type-I interferons (IFN-I). This function of pDCs is critical for effective antiviral defenses and has been implicated in autoimmunity. While IFN-I and select cytokines have been recognized as pDC secreted products, a comprehensive agnostic profiling of the...

In this study we sought to analyze the effects of genetic variants on gene regulation in a cell-state dependent manner during CD4 memory T cell activation. To do this, we performed an RNA-seq time series experiment on CD4 memory T cells activated with anti-CD3/CD28 beads in individuals with no autoimmune disease. We measured gene expression levels, and allele-specific expression at heterozygous sites...

We report the application of standard RNA-sequencing technology for high-throughput profiling of differential gene expression in mammalian cells. This study aims to compare differential gene expression in human monocytes in the absence or presence of HMGB1 and DMOG exposure would mimic hypoxia. Human monocytes (five million cells) from a healthy donor were divided into four groups in triplicate (control,...

RNA was extracted from FACS-sorted cells at 8 distinct stages of erythropoiesis, derived from CB- and PB-CD34+ cells. cDNA libraries were prepared using the Illumina TruSeq kit and sequenced on the Illumina HiSeq 2500 (Epigenomics Core of Weill Cornell Medical College, New York). This sequencing strategy produced ~15-80 million 50bp single end reads per sample. For each distinct stage of erythropoiesis,...

Includes both deidentified individual patient data and analysis outputs. Study included 56 patients. Demographic and clinical data including medication, diagnosis and Clinical Global Impression Severity (CGI-S) scales on outpatients who had COVID-19 between February 28th and October 1st 2020 were extracted from the electronic health records (EHR) from the hospital. Study observed a higher COVID-19...

The mutations that cause cancer cells to grow also confer specific vulnerabilities that normal cells lack. Some of these acquired alterations represent compelling therapeutic targets. The challenge is that, for the overwhelming majority of cancers, we do not fully understand the relationship between the genetic alterations of cancer and the dependencies they cause. To solve this problem, we are creating...

Background. Endometriosis is a common, complex disorder which is underrecognized and subject to prolonged delays in diagnosis. It is accompanied by significant changes in the eutopic endometrial lining. Methods. We have undertaken the first single cell RNA-sequencing (scRNA-Seq) comparison of endometrial tissues in freshly collected menstrual effluent (ME) from 33 subjects, including confirmed endometriosis...

We report the largest and most diverse genetic study of type 1 diabetes (T1D) to date (61,427 participants), yielding 78 genome-wide significant (P < 5 × 10−8) regions, including 36 novel. We define credible sets of T1D-associated variants and show they are enriched in immune cell-accessible chromatin, particularly CD4+ effector T cells. Using chromatin accessibility profiling of CD4+ T cells from...

Objective: We have investigated the molecular function of SCAMP5, a candidate risk gene for SLE exclusively expressed in plasmacytoid dendritic cells (pDCs) among peripheral leucocytes. Methods: We tested the independence of the association in SCAMP5 with SLE by performing conditional analyses. We profiled the expression pattern of SCAMP5 among circulating leucocytes at the transcript and protein...