Biology subjects

Henriksson, J.

Publications and source records attributed to Henriksson, J..

4 recordsLinked to original sources

bioRxiv2018

Reconstructing the human first trimester fetal-maternal interface using single cell transcriptomics

During the early weeks of human pregnancy, the fetal placenta implants into the uterine mucosa (decidua) where placental trophoblast cells intermingle and communicate with maternal cells. Here, we profile transcriptomes of [~]50,000 single cells from this unique microenvironment, sampling matched first trimester maternal blood and decidua, and fetal cells from the placenta itself. We define the cellular composition of human decidua, revealing five distinct subsets of decidual fibroblasts with differing growth factors and hormone production profiles, and show that fibroblast states define two distinct decidual layers. Among decidual NK cells, we resolve three subsets, each with a different immunomodulatory and chemokine profile. We develop a repository of ligand-receptor pairs (www.CellPhoneDB.org) and a statistical tool to predict the probability of cell-cell interactions via these pairs, highlighting specific interactions between decidual NK cells and invading fetal extravillous trophoblast cells, maternal immune and stromal cells. Our single cell atlas of the maternal-fetal interface reveals the cellular organization and interactions critical for placentation and reproductive success.

developmental biology↗

bioRxiv2017

The IRE1a-XBP1 pathway promotes T helper cell differentiation by resolving secretory stress and accelerating proliferation

The IRE1a-XBP1 pathway, a conserved adaptive mediator of the unfolded protein response, is indispensable for the development of secretory cells. It maintains endoplasmic reticulum homeostasis by facilitating protein folding and enhancing secretory capacity of the cells. Its role in immune cells is emerging. It is involved in dendritic cell, plasma cell and eosinophil development and differentiation. Using genome-wide approaches, integrating ChIPmentation and mRNA-sequencing data, we have elucidated the regulatory circuitry governed by the IRE1a-XBP1 pathway in type-2 T helper cells (Th2). We show that the XBP1 transcription factor is activated by splicing in vivo in T helper cell lineages. We report a comprehensive repertoire of XBP1 target genes in Th2 lymphocytes. We found that the pathway is conserved across cell types in terms of resolving secretory stress, and has T helper cell-specific functions in controlling activation-dependent Th2 cell proliferation and regulating cytokine expression in addition to secretion. These results provide a detailed picture of the regulatory map governed by the XBP1 transcription factor during Th2 lymphocyte activation.

cell biology↗

bioRxiv2017

FACSanadu: Graphical user interface for rapid visualization and quantification of flow cytometry data

MotivationFlow cytometry is a fundamental technique in cell biology, yet few open source packages are available to analyse these data. Here we describe FACSanadu, an interactive package for rapid visualization and measurement of flow cytometry data. It is the first open source package that can read length profile data from the COPAS Biosorter.\n\nAvailability and ImplementationFACSanadu is implemented in Java and uses the Qt framework for display. Binary distributions are made for all major operating systems (Windows, Macintosh, Linux). The source code and documentation is available as free software at http://www.facsanadu.org.\n\nContact: mahogny@areta.org

bioinformatics↗

bioRxiv2017

An unbiased reconstruction of the T helper cell type 2 differentiation network

T helper type 2 (Th2) cells are important regulators of our adaptive immune response, particularly the response against parasites, and have relevance for auto-immunity as well as tumour progression. This classic T helper type has been studied intensively, but not systematically. Using newly developed, genome-wide retroviral CRISPR knock-out (KO) technology, combined with RNA-seq, ATAC-seq and ChIP-seq, we have dissected the regulatory circuitry governing differentiation in these cells. During Th2 activation/differentiation approximately 4000 genes are perturbed, with at least 200 genes specifically associated with the Th2 program in mouse and human. We confirm previously known Th2 driver genes and have discovered several novel genes, including transcription factors, metabolic genes and potential receptors/cytokines, critical for Th2 function. Our study provides an atlas for, but not limited to, the Th2 regulatory network, pinpointing the key players of Th2 differentiation.

immunology↗