Single-cell trajectory detection uncovers progression and regulatory coordination in human B cell development.
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.
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.
Sean C
SC
Bendall
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.
Kara L
KL
Davis
Department of Biological Sciences, Department of Systems Biology, Columbia University, New York, NY 10027, USA.
El-Ad David
el-AD
Amir
Department of Biological Sciences, Department of Systems Biology, Columbia University, New York, NY 10027, USA.
Michelle D
MD
Tadmor
Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
Erin F
EF
Simonds
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.
Tiffany J
TJ
Chen
Department of Biological Sciences, Department of Systems Biology, Columbia University, New York, NY 10027, USA.
Daniel K
DK
Shenfeld
Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA. Electronic address: gnolan@stanford.edu.
Garry P
GP
Nolan
Department of Biological Sciences, Department of Systems Biology, Columbia University, New York, NY 10027, USA. Electronic address: dpeer@biology.columbia.edu.
Dana
D
Pe'er
D000465:Algorithms; D001402:B-Lymphocytes / Q000166:cytology*; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism; D038041:Lymphopoiesis; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology; D050799:STAT5 Transcription Factor / Q000378:metabolism; D060152:V(D)J Recombination
D015851:Interleukin-7; D050799:STAT5 Transcription Factor