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The Genetic Networks that Orchestrate Development of Specific Waves of Fetal and Adult B-1 and B-2 Development are Distinct

ABSTRACT: B lymphocyte development is often depicted as a linear process that initiates in the fetus and continues in the bone marrow after birth. Based on the dissection of B lymphopoiesis in a PU.1 hypomorphic strain of mice, generated by deletion of a 14kb upstream regulatory element of the Sfpi1 gene, and the transcriptional profiling of fetal and adult B cell progenitors, we establish the existence of three waves of B-1 and two waves of B-2 development and show that each of these waves has distinct transcriptional requirements. In addition to revealing an unappreciated complexity in the development of the humoral immune system, the results provide genetic evidence that the B-1 and B-2 lineages are distinct and a molecular basis for the layering of immune system development.

ORGANISM(S): Mus musculus

PROVIDER: GSE81411 | GEO | 2016/08/26

SECONDARY ACCESSION(S): PRJNA321487

REPOSITORIES: GEO

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Project description:The ability of cells to coordinately migrate in groups is crucial to enable them to travel long distances during embryonic development, wound healing and tumorigenesis, but the fundamental mechanisms underlying intercellular coordination during collective cell migration remain elusive despite considerable research efforts. A novel analytical framework is introduced here to explicitly detect and quantify cell clusters that move coordinately in a monolayer. The analysis combines and associates vast amount of spatiotemporal data across multiple experiments into transparent quantitative measures to report the emergence of new modes of organized behavior during collective migration of tumor and epithelial cells in wound healing assays. First, we discovered the emergence of a wave of coordinated migration propagating backward from the wound front, which reflects formation of clusters of coordinately migrating cells that are generated further away from the wound edge and disintegrate close to the advancing front. This wave emerges in both normal and tumor cells, and is amplified by Met activation with hepatocyte growth factor/scatter factor. Second, Met activation was found to induce coinciding waves of cellular acceleration and stretching, which in turn trigger the emergence of a backward propagating wave of directional migration with about an hour phase lag. Assessments of the relations between the waves revealed that amplified coordinated migration is associated with the emergence of directional migration. Taken together, our data and simplified modeling-based assessments suggest that increased velocity leads to enhanced coordination: higher motility arises due to acceleration and stretching that seems to increase directionality by temporarily diminishing the velocity components orthogonal to the direction defined by the monolayer geometry. Spatial and temporal accumulation of directionality thus defines coordination. The findings offer new insight and suggest a basic cellular mechanism for long-term cell guidance and intercellular communication during collective cell migration.

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The Genetic Networks that Orchestrate Development of Specific Waves of Fetal and Adult B-1 and B-2 Development are Distinct

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