1. Single-Cell Trajectory Detection Uncovers Progression and Regulatory Coordination in Human B Cell Development
- Author
-
Dana Pe'er, Garry P. Nolan, Daniel K. Shenfeld, Michelle D. Tadmor, Kara L. Davis, Erin F. Simonds, El-ad David Amir, Tiffany J. Chen, and Sean C. Bendall
- Subjects
Genetics ,B-Lymphocytes ,Biochemistry, Genetics and Molecular Biology(all) ,Interleukin-7 ,Lymphopoiesis ,Precursor Cells, B-Lymphoid ,V(D)J recombination ,Naive B cell ,Biology ,General Biochemistry, Genetics and Molecular Biology ,V(D)J Recombination ,Article ,Cell biology ,Haematopoiesis ,medicine.anatomical_structure ,medicine ,Transitional Cell ,STAT5 Transcription Factor ,Humans ,Stem cell ,Progenitor cell ,B cell ,Algorithms - Abstract
SummaryTissue 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.
- Full Text
- View/download PDF