Hematopoietic stem cell transplantation chemotherapy causes microglia senescence and peripheral macrophage engraftment in the brain.

Hematopoietic stem cell transplantation (HSCT) is a therapy used for multiple malignant and nonmalignant diseases, with chemotherapy used for pretransplantation myeloablation. The post-HSCT brain contains peripheral engrafted parenchymal macrophages, despite their absence in the normal brain, with the engraftment mechanism still undefined. Here we show that HSCT chemotherapy broadly disrupts mouse brain regenerative populations, including a permanent loss of adult neurogenesis. Microglial density was halved, causing microglial process expansion, coinciding with indicators of broad senescence. Although microglia expressed cell proliferation markers, they underwent cell cycle arrest in S phase with a majority expressing the senescence and antiapoptotic marker p21. In vivo single-cell tracking of microglia after recovery from chemical depletion showed loss of their regenerative capacity, subsequently replaced with donor macrophages. We propose that HSCT chemotherapy causes microglial senescence with a gradual decrease to a critical microglial density, providing a permissive niche for peripheral macrophage engraftment of the brain.

New Approach to Accelerated Image Annotation by Leveraging Virtual Reality and Cloud Computing.

Three-dimensional imaging is at the core of medical imaging and is becoming a standard in biological research. As a result, there is an increasing need to visualize, analyze and interact with data in a natural three-dimensional context. By combining stereoscopy and motion tracking, commercial virtual reality (VR) headsets provide a solution to this critical visualization challenge by allowing users to view volumetric image stacks in a highly intuitive fashion. While optimizing the visualization and interaction process in VR remains an active topic, one of the most pressing issue is how to utilize VR for annotation and analysis of data. Annotating data is often a required step for training machine learning algorithms. For example, enhancing the ability to annotate complex three-dimensional data in biological research as newly acquired data may come in limited quantities. Similarly, medical data annotation is often time-consuming and requires expert knowledge to identify structures of interest correctly. Moreover, simultaneous data analysis and visualization in VR is computationally demanding. Here, we introduce a new procedure to visualize, interact, annotate and analyze data by combining VR with cloud computing. VR is leveraged to provide natural interactions with volumetric representations of experimental imaging data. In parallel, cloud computing performs costly computations to accelerate the data annotation with minimal input required from the user. We demonstrate multiple proof-of-concept applications of our approach on volumetric fluorescent microscopy images of mouse neurons and tumor or organ annotations in medical images.