Expanded insights into COVID's biology, roots of repetitive behaviors, and mapping the developing mouse brain
Research Roundup: April 30, 2021
Welcome to the April 30, 2021 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.
Why some B cells are better against SARS-CoV-2
Research fellow Johannes Scheid, postdoctoral associate Basak Eraslan, core institute member Ramnik Xavier of the Immunology and Infectious Disease and Microbiome programs and Klarman Cell Observatory (KCO), and colleagues used single-cell RNA sequencing (scRNA-seq) and other methods to study blood samples from 14 people who recovered from COVID-19. They revealed distinct patterns of gene expression in B cells that produce antibodies that bind tightly to and neutralize SARS-CoV-2. They also discovered a new antibody, BG10-19, that neutralizes the virus, variants of concern such as the UK and South African variants, and the coronavirus that caused the 2003 SARS outbreak. The findings suggest some B cells are especially effective at producing antibodies, and offer insight on how to design antibodies against several coronaviruses. Read more in Cell and a Broad story.
Single-cell atlas of COVID-19 pathology built from autopsy samples
Researchers have found a range of molecular and genomic changes in individual SARS-CoV-2-infected cells from 17 patients who died of COVID-19. The team also saw signs of multiple, unsuccessful attempts by the lungs to repair themselves in response to respiratory failure. The team used scRNA-seq data from tissue samples taken from 11 organ systems — including the lungs, heart, liver, and kidneys — to build a comprehensive atlas of hundreds of thousands of individual cells showing how COVID-19 can lead to organ failure and death. Authors include Toni Delorey, Carly Ziegler, Graham Heimberg, Rachelly Normand, Yiming Yang, Asa Segerstolpe, Domenic Abbondanza, Stephen Fleming, Ayshwarya Subramanian, Daniel Montoro, Karthik Jagadeesh, Pritha Sen, Michal Slyper, Yered Pita-Juárez, Devan Phillips, Ioannis Vlachos, Alex Shalek, Alexandra-Chloé Villani, Orit Rozenblatt-Rosen, Aviv Regev, and many collaborators in the KCO; Cancer, Cell Circuits, and Immunology programs; Data Sciences Platform, and beyond. Read more in Nature, a Broad story, and news coverage in WBUR.
Transcriptomic changes associated with repetitive behaviors
Stereotypies, or extreme repetitive motor behaviors such as rocking, skin-picking, and sniffing, are symptoms of numerous psychiatric disorders and may also be induced through amphetamine exposure. In European Journal of Neuroscience, Stanley Center for Psychiatric Research associate member Ann Graybiel, Jill Crittenden (MIT), and colleagues use RNA-seq to study the transcriptomic changes associated with drug-induced repetitive behavior in mice. The team identified 20 genes that were dysregulated in mice with prolonged stereotypy, and found that many activated genes were regulated by neuregulin 1 signaling. Neuregulin 1 is a candidate gene for schizophrenia, suggesting a shared mechanism between stereotypy linked to the disorder and resulting from drug abuse. Read more in a McGovern Institute story.
Mouse mind map
A new atlas of mouse choroid plexus cells reveals cellular diversity, architecture, and signaling across brain ventricles during development, maturation, and aging of the choroid-plexus-brain barrier. A team including Neil Dani, Rebecca Herbst, Naomi Habib (Hebrew University of Jerusalem), Aviv Regev, and affiliate member Maria Lehtinen of the KCO and Boston Children’s Hospital constructed a single-cell and spatial atlas of each choroid plexus in the mouse brain at different stages. The map reveals ventricle- and age-dependent expression programs in epithelial and fibroblast cells; a common pool of progenitor cells for embryonic epithelial and neuronal cells; and cell-type specific interleukin-1 beta signaling in aged choroid plexus. The tissue is a potential entry point for SARS-CoV-2 virus in the brain. Read more in Cell.