Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, 10461, USA; The Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York, 10461, USA.
Institute for Oral Science, Matsumoto Dental University, Nagano, 399-0781 Japan.
Immunity. 2018 Oct 16;49(4):627-639.e6. doi: 10.1016/j.immuni.2018.08.019. Epub 2018 Oct 9.
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.
骨髓（BM）的非造血细胞部分经典上被鉴定为 CD45 Ter119 CD31（以下简称三阴性细胞或 TNCs）。尽管 TNCs 被认为包含异质的基质细胞群体，但它们的定义仍然不明确。在这里，我们表明，绝大多数 TNCs（约 85%）具有造血而非间充质来源。单细胞 RNA 测序揭示了 CD51 TNC 中的红细胞和淋巴祖细胞特征。Ly6D CD44 CD51 TNC 在表型和功能上类似于 CD45 前 B 淋巴样细胞，而 Ly6D CD44 CD51 TNC 则富含以前未被重视的位于前 CFU-E 和原红细胞之间的基质依赖性红细胞祖细胞。通过过继转移，CD44 CD51 TNC 有助于重新填充 B 淋巴细胞和红细胞区室。CD44 CD51 TNC 在苯肼诱导的急性溶血或镰状细胞贫血模型中也会扩增。这些发现因此揭示了具有生理相关性的新的基质相关功能性 CD45 造血祖细胞类群。
