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The bone marrow microenvironment at single-cell resolution

机译：单细胞分辨率下的骨髓微环境

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摘要

The bone marrow microenvironment has a key role in regulating haematopoiesis, but its molecular complexity and response to stress are incompletely understood. Here we map the transcriptional landscape of mouse bone marrow vascular, perivascular and osteoblast cell populations at single -cell resolution, both at homeostasis and under conditions of stress-induced haematopoiesis. This analysis revealed previously unappreciated levels of cellular heterogeneity within the bone marrow niche and resolved cellular sources of pro-haematopoietic growth factors, chemokines and membrane-bound ligands. Our studies demonstrate a considerable transcriptional remodelling of niche elements under stress conditions, including an adipocytic skewing of perivascular cells. Among the stress-induced changes, we observed that vascular Notch delta-like ligands (encoded by Dll1 and Dll4) were downregulated. In the absence of vascular Dll4, haematopoietic stem cells prematurely induced a myeloid transcriptional program. These findings refine our understanding of the cellular architecture of the bone marrow niche, reveal a dynamic and heterogeneous molecular landscape that is highly sensitive to stress and illustrate the utility of single-cell transcriptomic data in evaluating the regulation of haematopoiesis by discrete niche populations.
机译：骨髓微环境在调节血上具有关键作用，但其分子复杂性和对应力的反应是不完全理解的。在这里，我们将小鼠骨髓血管，血管和成骨细胞群的转录景观映射在稳态和应激诱导的血液杂种的条件下单一的单晶片分辨率。该分析揭示了骨髓内骨髓内骨髓内细胞内细胞异质性的先前未被覆富的细胞异质性水平，并分解了亲血管生长因子，趋化因子和膜结合配体的细胞来源。我们的研究表明，在胁迫条件下的利基元素的相当大的转录重塑，包括血管细胞的脂肪细胞偏斜。在应激诱导的变化中，我们观察到血管Notch Delta样配体（DLL1和DLL4编码）被下调。在没有血管DLL4的情况下，出血干细胞过早地诱导骨髓转录程序。这些发现优化了我们对骨髓利基的细胞结构的理解，揭示了对应力高度敏感的动态和异质的分子景观，并说明了单细胞转录组数据通过离散的利基群评估血吞噬子调节的效用。

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  • 来源
    《Nature》 |2019年第7755期|222-228|共7页
  • 作者

    Tikhonova Anastasia N.; Dolgalev Igor; Hu Hai; Sivaraj Kishor K.; Hoxha Edlira; Cuesta-Dominguez Alvaro; Pinho Sandra; Akhmetzyanova Ilseyar; Gao Jie; Witkowski Matthew; Guillamot Maria; Gutkin Michael C.; Zhang Yutong; Marier Christian; Diefenbach Catherine; Kousteni Stavroula; Heguy Adriana; Zhong Hua; Fooksman David R.; Butler Jason M.; Economides Aris; Frenette Paul S.; Adams Ralf H.; Satija Rahul; Tsirigos Aristotelis; Aifantis Iannis;

  • 作者单位

    NYU Sch Med Dept Pathol New York NY 10016 USA|NYU Sch Med Laura & Isaac Perlmutter Canc Ctr New York NY 10016 USA;

    NYU Sch Med Dept Pathol New York NY 10016 USA|NYU Sch Med Laura & Isaac Perlmutter Canc Ctr New York NY 10016 USA|NYU Sch Med Appl Bioinformat Labs New York NY 10016 USA;

    NYU Sch Med Dept Pathol New York NY 10016 USA|NYU Sch Med Laura & Isaac Perlmutter Canc Ctr New York NY 10016 USA;

    Max Planck Inst Mol Biomed Dept Tissue Morphogenesis Munster Germany|Univ Munster Fac Med Munster Germany;

    NYU Sch Med Dept Pathol New York NY 10016 USA|NYU Sch Med Laura & Isaac Perlmutter Canc Ctr New York NY 10016 USA;

    Columbia Univ Coll Phys & Surg Dept Physiol & Cellular Biophys New York NY USA;

    Albert Einstein Coll Med Ruth L & David S Gottesman Inst Stem Cell & Regen New York NY USA;

    Albert Einstein Coll Med Dept Pathol New York NY USA;

    Regeneron Genet Ctr Tarrytown NY USA;

    NYU Sch Med Dept Pathol New York NY 10016 USA|NYU Sch Med Laura & Isaac Perlmutter Canc Ctr New York NY 10016 USA;

    NYU Sch Med Dept Pathol New York NY 10016 USA|NYU Sch Med Laura & Isaac Perlmutter Canc Ctr New York NY 10016 USA;

    Hackensack Univ Med Ctr Ctr Discovery & Innovat Nutley NJ USA;

    NYU Sch Med Genome Technol Ctr Div Adv Res Technol New York NY USA;

    NYU Sch Med Genome Technol Ctr Div Adv Res Technol New York NY USA;

    NYU Sch Med Dept Pathol New York NY 10016 USA|NYU Sch Med Laura & Isaac Perlmutter Canc Ctr New York NY 10016 USA;

    Columbia Univ Coll Phys & Surg Dept Physiol & Cellular Biophys New York NY USA;

    NYU Sch Med Dept Pathol New York NY 10016 USA|NYU Sch Med Laura & Isaac Perlmutter Canc Ctr New York NY 10016 USA|NYU Sch Med Genome Technol Ctr Div Adv Res Technol New York NY USA;

    NYU Sch Med Div Biostatist Dept Populat Hlth New York NY USA;

    Albert Einstein Coll Med Dept Pathol New York NY USA;

    Hackensack Univ Med Ctr Ctr Discovery & Innovat Nutley NJ USA;

    Regeneron Genet Ctr Tarrytown NY USA;

    Albert Einstein Coll Med Ruth L & David S Gottesman Inst Stem Cell & Regen New York NY USA;

    Max Planck Inst Mol Biomed Dept Tissue Morphogenesis Munster Germany|Univ Munster Fac Med Munster Germany;

    New York Genome Ctr New York NY USA;

    NYU Sch Med Dept Pathol New York NY 10016 USA|NYU Sch Med Laura & Isaac Perlmutter Canc Ctr New York NY 10016 USA|NYU Sch Med Appl Bioinformat Labs New York NY 10016 USA;

    NYU Sch Med Dept Pathol New York NY 10016 USA|NYU Sch Med Laura & Isaac Perlmutter Canc Ctr New York NY 10016 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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