Ennis Sarah, Conforte Alessandra, O'Reilly Eimear, Takanlu Javid Sabour, Cichocka Tatiana, Dhami Sukhraj Pal, Nicholson Pamela, Krebs Philippe, Ó Broin Pilib, Szegezdi Eva
The SFI Centre for Research Training in Genomics Data Science, Galway, Ireland.
Discipline of Bioinformatics, School of Mathematical & Statistical Sciences, University of Galway, H91 TK33 Galway, Ireland.
iScience. 2023 May 23;26(6):106943. doi: 10.1016/j.isci.2023.106943. eCollection 2023 Jun 16.
The bone marrow (BM) is a complex microenvironment, coordinating the production of billions of blood cells every day. Despite its essential role and its relevance to hematopoietic diseases, this environment remains poorly characterized. Here we present a high-resolution characterization of the niche in health and acute myeloid leukemia (AML) by establishing a single-cell gene expression database of 339,381 BM cells. We found significant changes in cell type proportions and gene expression in AML, indicating that the entire niche is disrupted. We then predicted interactions between hematopoietic stem and progenitor cells (HSPCs) and other BM cell types, revealing a remarkable expansion of predicted interactions in AML that promote HSPC-cell adhesion, immunosuppression, and cytokine signaling. In particular, predicted interactions involving transforming growth factor β1 (TGFB1) become widespread, and we show that this can drive AML cell quiescence . Our results highlight potential mechanisms of enhanced AML-HSPC competitiveness and a skewed microenvironment, fostering AML growth.
骨髓（BM）是一个复杂的微环境，每天协调数十亿血细胞的生成。尽管其具有重要作用且与造血疾病相关，但该环境的特征仍不清楚。在这里，我们通过建立一个包含339,381个骨髓细胞的单细胞基因表达数据库，对健康和急性髓系白血病（AML）中的生态位进行了高分辨率表征。我们发现AML中细胞类型比例和基因表达有显著变化，表明整个生态位被破坏。然后，我们预测了造血干细胞和祖细胞（HSPCs）与其他骨髓细胞类型之间的相互作用，揭示了AML中预测的促进HSPC-细胞粘附、免疫抑制和细胞因子信号传导的相互作用显著增加。特别是，涉及转化生长因子β1（TGFB1）的预测相互作用变得广泛，并且我们表明这可以驱动AML细胞静止。我们的结果突出了增强AML-HSPC竞争力和微环境失衡的潜在机制，促进了AML的生长。
