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 language | English (US) |
|---|---|
| Pages (from-to) | 627-639.e6 |
| Journal | Immunity |
| Volume | 49 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 16 2018 |
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ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases
Cite this
The Majority of CD45– Ter119– CD31– Bone Marrow Cell Fraction Is of Hematopoietic Origin and Contains Erythroid and Lymphoid Progenitors. / Boulais, Philip E.; Mizoguchi, Toshihide; Zimmerman, Samuel; Nakahara, Fumio; Vivié, Judith; Mar, Jessica C.; van Oudenaarden, Alexander; Frenette, Paul S.
In: Immunity, Vol. 49, No. 4, 16.10.2018, p. 627-639.e6.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The Majority of CD45– Ter119– CD31– Bone Marrow Cell Fraction Is of Hematopoietic Origin and Contains Erythroid and Lymphoid Progenitors
AU - Boulais, Philip E.
AU - Mizoguchi, Toshihide
AU - Zimmerman, Samuel
AU - Nakahara, Fumio
AU - Vivié, Judith
AU - Mar, Jessica C.
AU - van Oudenaarden, Alexander
AU - Frenette, Paul S.
PY - 2018/10/16
Y1 - 2018/10/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85055072485&partnerID=8YFLogxK
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U2 - 10.1016/j.immuni.2018.08.019
DO - 10.1016/j.immuni.2018.08.019
M3 - Article
VL - 49
SP - 627-639.e6
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 4
ER -