Emergence of the erythroid lineage from multipotent hematopoiesis [preprint]

Red cell formation begins with the hematopoietic stem cell, but the manner by which it gives rise to erythroid progenitors, and their subsequent developmental path, remain unclear. Here we combined single-cell transcriptomics of murine hematopoietic tissues with fate potential assays to infer a continuous yet hierarchical structure for the hematopoietic network. We define the erythroid differentiation trajectory as it emerges from multipotency and diverges from 6 other blood lineages. With the aid of a new flow-cytometric sorting strategy, we validated predicted cell fate potentials at the single cell level, revealing a coupling between erythroid and basophil/mast cell fates. We uncovered novel growth factor receptor regulators of the erythroid trajectory, including the proinflammatory IL- 17RA, found to be a strong erythroid stimulator; and identified a global hematopoietic response to stress erythropoiesis. We further identified transcriptional and high-purity FACS gates for the complete isolation of all classically-defined erythroid burst-forming (BFU-e) and colony-forming progenitors (CFU-e), finding that they express a dedicated transcriptional program, distinct from that of terminally-differentiating erythroblasts. Intriguingly, profound remodeling of the cell cycle is intimately entwined with CFU-e developmental progression and with a sharp transcriptional switch that extinguishes the CFU-e stage and activates terminal differentiation. Underlying these results, our work showcases the utility of theoretic approaches linking transcriptomic data to predictive fate models, providing key insights into lineage development in vivo

The Kilopixel Array Pathfinder Project (KAPPa), a 16 pixel integrated heterodyne focal plane array

KAPPa (the Kilopixel Array Pathfinder Project) is developing key technologies to enable the construction of heterodyne focal plane arrays in the terahertz frequency regime with ~1000 pixels. The leap to ~1000 pixels requires solutions to several key technological problems before the construction of such a focal plane is possible. The KAPPa project will develop a small (16-pixel) 2D integrated heterodyne focal plane array for the 660 GHz atmospheric window as a technological pathfinder towards future kilopixel heterodyne focal plane arrays

Results of using permanent magnets to suppress Josephson noise in the KAPPa SIS receiver

We present the results from the magnetic field generation within the Kilopixel Array Pathfinder Project (KAPPa) instrument. The KAPPa instrument is a terahertz heterodyne receiver using a Superconducting-Insulating- Superconducting (SIS) mixers. To improve performance, SIS mixers require a magnetic field to suppress Josephson noise. The KAPPa test receiver can house a tunable electromagnet used to optimize the applied magnetic field. The receiver is also capable of accommodating a permanent magnet that applies a fixed field. Our permanent magnet design uses off-the-shelf neodymium permanent magnets and then reshapes the magnetic field using machined steel concentrators. These concentrators allow the use of an unmachined permanent magnet in the back of the detector block while two small posts provide the required magnetic field across the SIS junction in the detector cavity. The KAPPa test receiver is uniquely suited to compare the permanent magnet and electromagnet receiver performance. The current work includes our design of a ‘U’ shaped permanent magnet, the testing and calibration procedure for the permanent magnet, and the overall results of the performance comparison between the electromagnet and the permanent magnet counterpart

Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

Abstract:Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 – affects olfaction directly, by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing demonstrated that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing revealed that ACE2 is expressed in support cells, stem cells, and perivascular cells, rather than in neurons. Immunostaining confirmed these results and revealed pervasive expression of ACE2 protein in dorsally-located olfactory epithelial sustentacular cells and olfactory bulb pericytes in the mouse. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients