Introduction

Tissue regeneration is an orchestrated progression of cells from an immature state to a mature one, conventionally represented as distinctive cell subsets. A continuum of transitional cell states exists between these discrete stages. We combine the depth of single-cell mass cytometry and an algorithm developed to leverage this continuum by aligning single cells of a given lineage onto a unified trajectory that accurately predicts the developmental path de novo. Applied to human B cell lymphopoiesis, the algorithm (termed Wanderlust) constructed trajectories spanning from hematopoietic stem cells through to naive B cells. This trajectory revealed nascent fractions of B cell progenitors and aligned them with developmentally cued regulatory signaling including IL-7/STAT5 and cellular events such as immunoglobulin rearrangement, highlighting checkpoints across which regulatory signals are rewired paralleling changes in cellular state. This study provides a comprehensive analysis of human B lymphopoiesis, laying a foundation to apply this approach to other tissues and "corrupted" developmental processes including cancer.

Publications

  1. Single-cell trajectory detection uncovers progression and regulatory coordination in human B cell development.
    Cite this
    Bendall SC, Davis KL, Amir el-AD, Tadmor MD, Simonds EF, Chen TJ, Shenfeld DK, Nolan GP, Pe'er D, 2014-04-01 - Cell

Credits

  1. Sean C Bendall
    Developer

    Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, United States of America

  2. Kara L Davis
    Developer

    Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, United States of America

  3. El-ad David Amir
    Developer

    Department of Biological Sciences, Department of Systems Biology, United States of America

  4. Michelle D Tadmor
    Developer

    Department of Biological Sciences, Department of Systems Biology, United States of America

  5. Erin F Simonds
    Developer

    Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, United States of America

  6. Tiffany J Chen
    Developer

    Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, United States of America

  7. Daniel K Shenfeld
    Developer

    Department of Biological Sciences, Department of Systems Biology, United States of America

  8. Garry P Nolan
    Developer

    Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, United States of America

  9. Dana Pe'er
    Investigator

    Department of Biological Sciences, Department of Systems Biology, United States of America

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Summary
AccessionBT006352
Tool TypeApplication
Category
Platforms
Technologies
User InterfaceTerminal Command Line
Download Count0
Country/RegionUnited States of America
Submitted ByDana Pe'er