ABSTRACT
Individual cells make decisions that are adapted to their internal state and surroundings, but how cells can reliably do this remains unclear. To study the information processing capacity of human cells, we conducted multiplexed quantification of signaling responses and markers of the cellular state. Signaling nodes in a network displayed adaptive information processing, which led to heterogeneous growth factor responses and enabled nodes to capture partially nonredundant information about the cellular state. Collectively, as a multimodal percept this gives individual cells a large information processing capacity to accurately place growth factor concentration within the context of their cellular state and make cellular state-dependent decisions. Heterogeneity and complexity in signaling networks may have coevolved to enable specific and context-aware cellular decision-making in a multicellular setting.
Subject(s)
Signal Transduction , Single-Cell Analysis , Epidermal Growth Factor/pharmacology , Epithelial Cells/drug effects , Epithelial Cells/physiology , HumansABSTRACT
Advancing age causes reduced hippocampal neurogenesis, associated with age-related cognitive decline. The spatial relationship of age-induced alterations in neural stem cells (NSCs) and surrounding cells within the hippocampal niche remains poorly understood due to limitations of antibody-based cellular phenotyping. We established iterative indirect immunofluorescence imaging (4i) in tissue sections, allowing for simultaneous detection of 18 proteins to characterize NSCs and surrounding cells in 2-, 6-, and 12-month-old mice. We show that reorganization of the dentate gyrus (DG) niche already occurs in middle-aged mice, paralleling the decline in neurogenesis. 4i-based tissue analysis of the DG identifies changes in cell-type contributions to the blood-brain barrier and microenvironments surrounding NSCs to play a pivotal role to preserve neurogenic permissiveness. The data provided represent a resource to characterize the principles causing alterations of stem cell-associated plasticity within the aging DG and provide a blueprint to analyze somatic stem cell niches across lifespan in complex tissues.
Subject(s)
Aging , Dentate Gyrus/cytology , Neural Stem Cells/physiology , Neurogenesis/physiology , Animals , Blood-Brain Barrier , Brain/embryology , Dentate Gyrus/diagnostic imaging , Dentate Gyrus/embryology , Dentate Gyrus/metabolism , Female , Fluorescent Antibody Technique , Human Embryonic Stem Cells , Humans , Male , Mice, Inbred C57BL , Organoids , Proteins/analysis , Stem Cell NicheABSTRACT
The application and integration of molecular profiling technologies create novel opportunities for personalized medicine. Here, we introduce the Tumor Profiler Study, an observational trial combining a prospective diagnostic approach to assess the relevance of in-depth tumor profiling to support clinical decision-making with an exploratory approach to improve the biological understanding of the disease.
