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Cell. 2014 Apr 24;157(3):714-25. doi: 10.1016/j.cell.2014.04.005.

Single-cell trajectory detection uncovers progression and regulatory coordination in human B cell development.

Author information

1
Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
2
Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA; Hematology and Oncology, Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
3
Department of Biological Sciences, Department of Systems Biology, Columbia University, New York, NY 10027, USA.
4
Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
5
Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA; Program in Biomedical Informatics, Stanford University, Stanford, CA 94305, USA; Department of Computer Science, Stanford University, Stanford, CA 94305, USA.
6
Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA. Electronic address: gnolan@stanford.edu.
7
Department of Biological Sciences, Department of Systems Biology, Columbia University, New York, NY 10027, USA. Electronic address: dpeer@biology.columbia.edu.

Abstract

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.

PMID:
24766814
PMCID:
PMC4045247
DOI:
10.1016/j.cell.2014.04.005
[Indexed for MEDLINE]
Free PMC Article

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