A Common Origin for B-1a and B-2 Lymphocytes in Clonal Pre- Hematopoietic Stem Cells

Brandon K. Hadland, Barbara Varnum-Finney, Pankaj K. Mandal, Derrick J. Rossi, Michael G. Poulos, Jason M. Butler, Shahin Rafii, Mervin Yoder, Momoko Yoshimoto, Irwin D. Bernstein

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Recent evidence points to the embryonic emergence of some tissue-resident innate immune cells, such as B-1a lymphocytes, prior to and independently of hematopoietic stem cells (HSCs). However, whether the full hematopoietic repertoire of embryonic HSCs initially includes these unique lineages of innate immune cells has been difficult to assess due to lack of clonal assays that identify and assess HSC precursor (pre-HSC) potential. Here, by combining index sorting of single embryonic hemogenic precursors with in vitro HSC maturation and transplantation assays, we analyze emerging pre-HSCs at the single-cell level, revealing their unique stage-specific properties and clonal lineage potential. Remarkably, clonal pre-HSCs detected between E9.5 and E11.5 contribute to the complete B cell repertoire, including B-1a lymphocytes, revealing a previously unappreciated common precursor for all B cell lineages at the pre-HSC stage and a second embryonic origin for B-1a lymphocytes.

Original languageEnglish (US)
Pages (from-to)1563-1572
Number of pages10
JournalStem Cell Reports
Volume8
Issue number6
DOIs
StatePublished - Jun 6 2017

Keywords

  • AGM
  • B lymphocyte
  • B-1a cell
  • hematopoietic stem cell
  • pre-HSC

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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    Hadland, B. K., Varnum-Finney, B., Mandal, P. K., Rossi, D. J., Poulos, M. G., Butler, J. M., Rafii, S., Yoder, M., Yoshimoto, M., & Bernstein, I. D. (2017). A Common Origin for B-1a and B-2 Lymphocytes in Clonal Pre- Hematopoietic Stem Cells. Stem Cell Reports, 8(6), 1563-1572. https://doi.org/10.1016/j.stemcr.2017.04.007