The anatomy of the mammalian visual system, from the retina to the neocortex, is organized hierarchically1. However, direct observation of cellular-level functional interactions across this hierarchy is lacking due to the challenge of simultaneously recording activity across numerous regions. Here we describe a large, open dataset—part of the Allen Brain Observatory2—that surveys spiking from tens of thousands of units in…
Antibodies are a potential therapy for SARS-CoV-2, but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to SARS-CoV-2’s receptor-binding domain (RBD) affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino-acid mutation that fully escapes the REGN-COV2 cocktail, which consists of…
Hydrogel biomaterials derived from natural biopolymers (e.g., fibrin, collagen, decellularized extracellular matrix) are regularly utilized in three-dimensional (3D) cell culture and tissue engineering. In contrast to those based on synthetic polymers, natural materials permit enhanced cytocompatibility, matrix remodeling, and biological integration. Despite these advantages, natural protein-based gels have lagged behind synthetic alternatives in their tunability; methods to selectively modulate the…
Autologous, CCR5 gene-edited hematopoietic stem and progenitor cell (HSPC) transplantation is a promising strategy for achieving HIV remission. However, only a fraction of HSPCs can be edited ex vivo to provide protection against infection. To project the thresholds of CCR5-edition necessary for HIV remission, we developed a mathematical model that recapitulates blood T cell reconstitution and plasma simian-HIV (SHIV) dynamics…
Neutrophils are the most abundant leukocytes in circulation and the first responders to infectious and sterile inflammation, including skin exposure to ultraviolet (UV) light. We demonstrate that neutrophils not only migrate to the UV light–exposed skin but also disseminate systemically. In the kidney, neutrophils mediate inflammatory and injury responses triggered by skin exposure to UV. They had a proinflammatory phenotype:…
Processing within the anterior cingulate cortex (ACC) is crucial for the patterning of appropriate behavior, and ACC dysfunction following chronic drug use is thought to play a major role in drug addiction. However, cortical pyramidal projection neurons can be subdivided into two major types (intratelencephalic (IT) and pyramidal tract (PT)), with distinct inputs and projection targets, molecular and receptor profiles,…
Skin epithelium can accumulate a high burden of oncogenic mutations without morphological or functional consequences. To investigate the mechanism of oncogenic tolerance, we induced HrasG12V in single murine epidermal cells and followed them long-term. We observed that HrasG12V promotes an early and transient clonal expansion driven by increased progenitor renewal that is replaced with an increase in progenitor differentiation leading to reduced…
The core of the mammalian circadian clock mechanism is a time-delayed transcription-translation feedback loop (TTFL), which influences the transcription and expression of a large fraction of the transcriptome. Through this mechanism, the mammalian circadian clock modulates many physiological functions, including the timing of cell division and rates of metabolism in specific tissues. Circadian clock dysfunction is associated with several human…
Single-cell RNA-sequencing (scRNA-seq) has become an essential tool for characterizing gene expression in eukaryotes but current methods are incompatible with bacteria. Here, we introduce microSPLiT, a high-throughput scRNA-seq method for gram-negative and gram-positive bacteria that can resolve heterogeneous transcriptional states. We applied microSPLiT to >25,000 Bacillus subtilis cells sampled at different growth stages, creating an atlas of changes in metabolism and lifestyle.…
Engineering chimeric antigen receptors (CAR) or T cell receptors (TCR) helps create disease-specific T cells for targeted therapy, but the cost and rigor associated with manufacturing engineered T cells ex vivo can be prohibitive, so programing T cells in vivo may be a viable alternative. Here we report an injectable nanocarrier that delivers in vitro-transcribed (IVT) CAR or TCR mRNA…