Journal
CELL
Volume 157, Issue 3, Pages 714-725Publisher
CELL PRESS
DOI: 10.1016/j.cell.2014.04.005
Keywords
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Categories
Funding
- St. Baldrick's Foundation Scholar Award
- Alex's Lemonade Stand Young Investigator Award
- Lucile Packard Foundation for Children's Health
- NIH-NCATS-CTSA [UL1 TR001085]
- Child Health Research Institute of Stanford University
- Damon Runyon Cancer Research Foundation Fellowship [DRG-2017-09]
- NIH [K99GM104148-01, S10 SIG S10RR027582-01, 152175.5041015.0412, DP2-OD002414-01, U54CA121852-01A1]
- National Defense Science & Engineering Graduate Fellowship Program
- Stanford University Graduate Fellowship
- Google Anita Borg Memorial Scholarship
- William Lawrence and Blanche Hughes Foundation
- Entertainment Industry Foundation
- Northrup-Grumman Corp
- Alliance for Lupus Research
- Lymphoma Research Foundation
- Bill and Melinda Gates Foundation
- NSF [MCB-1149728]
- Packard Fellowship for Science and Engineering
- [0158 G KB065]
- [1R01CA130826]
- [5U54CA143907NIH]
- [CIRM: DR1-01477]
- [HEALTH.2010.1.2-1]
- [HHSF223201210194C - FDA: BAA-12-00118]
- [HHSN272200700038C]
- [N01-HV-00242]
- [NIH 41000411217]
- [NIH 5-24927]
- [P01 CA034233-22A1]
- [PN2EY018228]
- [RB2-01592]
- [U19 AI057229]
- [U54CA149145]
- [W81XWH-12-1-0591]
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1149728] Funding Source: National Science Foundation
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Tissue regeneration is an orchestrated progression of cells from an immature state to amature 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 continuumby 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.
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