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

被引:32
作者
Boulais, Philip E. [1 ,3 ]
Mizoguchi, Toshihide [4 ,10 ]
Zimmerman, Samuel [3 ,5 ]
Nakahara, Fumio [1 ,3 ]
Vivie, Judith [6 ,7 ]
Mar, Jessica C. [3 ,5 ,8 ,9 ]
van Oudenaarden, Alexander [6 ,7 ]
Frenette, Paul S. [1 ,2 ,3 ]
机构
[1] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA
[2] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA
[3] Albert Einstein Coll Med, Ruth L & David S Gottesman Inst Stem Cell & Regen, Bronx, NY 10461 USA
[4] Matsumoto Dent Univ, Inst Oral Sci, Nagano 3990781, Japan
[5] Albert Einstein Coll Med, Dept Syst & Computat Biol, Bronx, NY 10461 USA
[6] KNAW Royal Netherlands Acad Arts & Sci, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands
[7] Univ Med Ctr Utrecht, Canc Genom Netherlands, NL-3584 CT Utrecht, Netherlands
[8] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA
[9] Univ Queensland, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld 4072, Australia
[10] Tokyo Dent Coll, Oral Hlth Sci Ctr, Tokyo 1010061, Japan
基金
日本学术振兴会;
关键词
MESENCHYMAL STEM-CELLS; B-CELL; TRANSCRIPTOME ANALYSES; MOUSE MODEL; DIFFERENTIATION; NICHES; MARKS; MICE; ERYTHROPOIESIS; SPECIFICATION;
D O I
10.1016/j.immuni.2018.08.019
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 proery-throblasts. 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.
引用
收藏
页码:627 / +
页数:19
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