Ly6d marks the earliest stage of B-cell specification and identifies the branchpoint between B-cell and T-cell development

  1. Matthew A. Inlay1,7,8,
  2. Deepta Bhattacharya2,7,
  3. Debashis Sahoo3,
  4. Thomas Serwold1,
  5. Jun Seita1,
  6. Holger Karsunky4,
  7. Sylvia K. Plevritis5,
  8. David L. Dill6 and
  9. Irving L. Weissman1
  1. 1Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA;
  2. 2Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA;
  3. 3Department of Electrical Engineering, Stanford University, Stanford, California 94305, USA;
  4. 4Cellerant Therapeutics, San Carlos, California 94070, USA;
  5. 5Department of Radiology, Stanford University, Stanford, California 94305, USA;
  6. 6Department of Computer Science, Stanford University, Stanford, California 94305, USA
    1. 7 These authors contributed equally to this work.

    Abstract

    Common lymphoid progenitors (CLPs) clonally produce both B- and T-cell lineages, but have little myeloid potential in vivo. However, some studies claim that the upstream lymphoid-primed multipotent progenitor (LMPP) is the thymic seeding population, and suggest that CLPs are primarily B-cell-restricted. To identify surface proteins that distinguish functional CLPs from B-cell progenitors, we used a new computational method of Mining Developmentally Regulated Genes (MiDReG). We identified Ly6d, which divides CLPs into two distinct populations: one that retains full in vivo lymphoid potential and produces more thymocytes at early timepoints than LMPP, and another that behaves essentially as a B-cell progenitor.

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