Differentiation, self-renewal and quiescence of Hematopoietic stem cells (HSCs) is tightly regulated in order to protect the HSCs from the strain of constant cell division and depletion of the stem cell pool. The neurotransmitter Neuropeptide Y (NPY) is released from sympathetic nerves in the bone marrow and has been shown to indirectly affect HSC function through effects on bone marrow (BM) multipotent Mesenchymal Stromal Cells (MSCs), osteoblasts (OBs) and macrophages. Although the absence of NPY has been shown to be accompanied by severe BM impairment and delayed engraftment of HSCs, the direct effects of NPY on HSCs have never been assessed. Here, we aimed to explore the effect of NPY on the regulation of HSCs. All NPY receptors Y1, Y2, Y4 and Y5 were found to be highly expressed on most HSCs and mature hematopoietic cell subsets. In culture, in particularly expression of the Y1 receptor was shown to decrease in time. Doses of 300 nM NPY suppressed HSC proliferation in cell cultures, as confirmed by an increase of HSCs in G0 phase and an increase in the gene expression levels of FOXO3, DICER1, SMARCA2 and PDK1, which all have been shown to play an important role in the regulation of cell quiescence. These data support the idea that NPY may have a direct effect on the regulation of HSC fate by modulating cell quiescence.

中文翻译：

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神经肽Y参与造血干细胞静止的调节

造血干细胞 (HSC) 的分化、自我更新和静止受到严格调控，以保护 HSC 免受持续细胞分裂和干细胞库耗竭的影响。神经递质神经肽 Y (NPY) 从骨髓中的交感神经释放，并已被证明通过影响骨髓 (BM) 多能间充质基质细胞 (MSC)、成骨细胞 (OB) 和巨噬细胞间接影响 HSC 功能。尽管 NPY 的缺失已被证明伴有严重的 BM 损伤和 HSC 的移植延迟，但从未评估过 NPY 对 HSC 的直接影响。在这里，我们旨在探讨 NPY 对 HSC 调节的影响。发现所有 NPY 受体 Y1、Y2、Y4 和 Y5 在大多数 HSC 和成熟的造血细胞亚群上高度表达。在文化上，特别是 Y1 受体的表达显示出随时间减少。300 nM NPY 的剂量抑制了细胞培养物中的 HSC 增殖，这通过 G0 期 HSC 的增加和 FOXO3、DICER1、SMARCA2 和 PDK1 的基因表达水平的增加得到证实，这些都已被证明在细胞静止的调节。这些数据支持这样的观点，即 NPY 可能通过调节细胞静止对 HSC 命运的调节产生直接影响。