The Majority of CD45 Ter119 CD31 Bone Marrow Cell Fraction Is of Hematopoietic Origin and Contains Erythroid and Lymphoid Progenitors

Philip E. Boulais, Toshihide Mizoguchi, Samuel Zimmerman, Fumio Nakahara, Judith Vivié, Jessica C. Mar, Alexander van Oudenaarden, Paul S. Frenette

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The non-hematopoietic cell fraction of the bone marrow (BM) is classically identified as CD45 Ter119 CD31 (herein referred to as triple-negative cells or TNCs). Although TNCs are believed to contain heterogeneous stromal cell populations, they remain poorly defined. Here we showed that the vast majority of TNCs (∼85%) have a hematopoietic rather than mesenchymal origin. Single cell RNA-sequencing revealed erythroid and lymphoid progenitor signatures among CD51 TNCs. Ly6D+ CD44+ CD51 TNCs phenotypically and functionally resembled CD45+ pro-B lymphoid cells, whereas Ly6D CD44+ CD51 TNCs were enriched in previously unappreciated stromal-dependent erythroid progenitors hierarchically situated between preCFU-E and proerythroblasts. Upon adoptive transfer, CD44+ CD51 TNCs contributed to repopulate the B-lymphoid and erythroid compartments. CD44+ CD51 TNCs also expanded during phenylhydrazine-induced acute hemolysis or in a model of sickle cell anemia. These findings thus uncover physiologically relevant new classes of stromal-associated functional CD45 hematopoietic progenitors. Bone marrow triple-negative CD45 Ter119 CD31 cells are thought to contain heterogeneous stromal cell populations. Boulais et al. show these cells are mostly hematopoietic in origin and contain previously unappreciated stromal-associated erythroid and B-lymphoid progenitor populations.

Original languageEnglish (US)
Pages (from-to)627-639.e6
JournalImmunity
Volume49
Issue number4
DOIs
StatePublished - Oct 16 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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