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 journal/periodicalArticleScientificpeer-review

25 Citations (Scopus)

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.

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

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