Exploring the tumor micro-environment in primary and metastatic tumors of different ovarian cancer histotypes.

Ovarian cancer is a highly heterogeneous disease consisting of at least five different histological subtypes with varying clinical features, cells of origin, molecular composition, risk factors, and treatments. While most single-cell studies have focused on High grade serous ovarian cancer, a comprehensive landscape of the constituent cell types and their interactions within the tumor microenvironment are yet to be established in the different ovarian cancer histotypes. Further characterization of tumor progression, metastasis, and various histotypes are also needed to connect molecular signatures to pathological grading for personalized diagnosis and tailored treatment.

Engineered exosomes targeting MYC reverse the proneural-mesenchymal transition and extend survival of glioblastoma.

Dysregulated Myc signaling is a key oncogenic pathway in glioblastoma multiforme (GBM). Yet, effective therapeutic targeting of Myc continues to be challenging. Here, we demonstrate that exosomes generated from human bone marrow mesenchymal stem cells (MSCs) engineered to encapsulate siRNAs targeting Myc (iExo-Myc) localize to orthotopic GBM tumors in mice.

A molecular atlas of the human postmenopausal fallopian tube and ovary from single-cell RNA and ATAC sequencing.

As part of the Human Cell Atlas Initiative, our goal is to generate single-cell transcriptomics (single-cell RNA sequencing [scRNA-seq], 86,708 cells) and regulatory (single-cell assay on transposase accessible chromatin sequencing [scATAC-seq], 59,830 cells) profiles of the normal postmenopausal ovary and fallopian tube (FT). The FT contains 11 major cell types, and the ovary contains 6. The dominating cell type in the FT and ovary is the stromal cell, which expresses aging-associated genes.

Characterizing the tumor microenvironment of metastatic ovarian cancer by single-cell transcriptomics.

Understanding the cellular composition of the tumor microenvironment and the interactions of the cells is essential to the development of successful immunotherapies in cancer. We perform single-cell RNA sequencing (scRNA-seq) of 9,885 cells isolated from the omentum in 6 patients with ovarian cancer and identify 9 major cell types, including cancer, stromal, and immune cells. Transcriptional analysis of immune cells stratifies our patient samples into 2 groups: (1) high T cell infiltration (high T) and (2) low T cell infiltration (low T).

Development of a novel human recellularized endometrium that responds to a 28-day hormone treatment.

Three-dimensional (3D) in vitro models have been established to study the physiology and pathophysiology of the endometrium. With emerging evidence that the native extracellular matrix (ECM) provides appropriate cues and growth factors essential for tissue homeostasis, we describe, a novel 3D endometrium in vitro model developed from decellularized human endometrial tissue repopulated with primary endometrial cells. Analysis of the decellularized endometrium using mass spectrometry revealed an enrichment of cell adhesion molecules, cytoskeletal proteins, and ECM proteins such as collagen IV and laminin.

A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle.

The endocrine system dynamically controls tissue differentiation and homeostasis, but has not been studied using dynamic tissue culture paradigms. Here we show that a microfluidic system supports murine ovarian follicles to produce the human 28-day menstrual cycle hormone profile, which controls human female reproductive tract and peripheral tissue dynamics in single, dual and multiple unit microfluidic platforms (Solo-MFP, Duet-MFP and Quintet-MPF, respectively). These systems simulate the in vivo female reproductive tract and the endocrine loops between organ modules for the ovary, fallopian tube, uterus, cervix and liver, with a sustained circulating flow between all tissues.

B cells expressing IFN-γ suppress Treg-cell differentiation and promote autoimmune experimental arthritis.

Clinical efficacy in the treatment of rheumatoid arthritis with anti-CD20 (Rituximab)-mediated B-cell depletion has garnered interest in the mechanisms by which B cells contribute to autoimmunity. We have reported that B-cell depletion in a murine model of proteoglycan-induced arthritis (PGIA) leads to an increase in Treg cells that correlate with decreased autoreactivity. Here, we demonstrate that the increase in Treg cells after B-cell depletion is due to an increase in the differentiation of naïve CD4(+) T cells into Treg cells.

Tissue specific CD4+ T cell priming determines the requirement for interleukin-23 in experimental arthritis.

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease with striking heterogeneity in (i) clinical presentation, (ii) autoantibody profiles and (iii) responses to treatment suggesting that distinct molecular mechanisms may underlie the disease process. Proteoglycan-induced arthritis (PGIA) is induced by two pathways either by intraperitoneal (i.p.

B cell-specific expression of inducible costimulator ligand is necessary for the induction of arthritis in mice.

Objective: Inducible costimulator (ICOS)-ICOSL interactions are necessary for activation of Teff cells and follicular helper T (Tfh) cells. ICOSL is expressed on B cells, macrophages, and dendritic cells and can be induced on nonhematopoietic cells. The aim of this study was to determine whether expression of ICOSL on B cells is necessary for the development of proteoglycan (PG)-induced arthritis (PGIA).

Location of CD4+ T cell priming regulates the differentiation of Th1 and Th17 cells and their contribution to arthritis.

Th cytokines IFN-γ and IL-17 are linked to the development of autoimmune disease. In models of rheumatoid arthritis, that is, proteoglycan (PG)-induced arthritis, IFN-γ is required, whereas in collagen-induced arthritis, IL-17 is necessary for development of arthritis. In this study we show that the route of immunization determines the requirement for either IFN-γ or IL-17 in arthritis.