Hallmarks and Regulatory Coordination Points in Human Development Revealed by Single Cell Trajectory DetectionThursday, 18 September 2014 at 14:30 Add to Calendar ▼2014-09-18 14:30:002014-09-18 15:30:00Europe/LondonHallmarks and Regulatory Coordination Points in Human Development Revealed by Single Cell Trajectory DetectionExosomes and Single Cell Analysis Summit in San Diego, California, USASan Diego, California, USASELECTBIOenquiries@selectbiosciences.com Tissue regeneration is an orchestrated progression of cells from an immature state to a mature one, conventionally represented as distinctive cell subsets landmarked along development. Yet, a continuum of transitional cell states is exists between these discretized stages. We combine the deep phenotyping of single-cell mass cytometry to leverage this continuum by aligning cells of a given lineage onto a unified trajectory that accurately predicts the developmental path de novo. Applied to primary human B-cell lymphopoiesis, the algorithm (termed Wanderlust) constructed trajectories spanning from hematopoietic stem cells through to naïve B cells. Analysis of this trajectory revealed nascent fractions of B-cell progenitors and aligned them with developmentally cued regulatory signaling (IL-7/STAT5) and cellular events (immunoglobulin rearrangement), highlighting developmental checkpoints across which regulatory signals are rewired paralleling changes in cellular state. This study provides the most comprehensive phenotypic analysis of human B lymphopoiesis to date, laying a foundation to apply such methods to other tissue types and “corrupted” developmental processes such as cancer. |