美国哥伦比亚大学欧文医学中心Emmanuelle Passegué研究组的最新研究，揭示了肿瘤坏死因子α（TNF-α）协调造血干细胞（HSC）生存和骨髓再生机制。相关论文于2019年9月发表在《细胞—干细胞》上。

研究发现TNF-α对HSC和祖细胞的作用不同，促进造血清除和再生。研究人员表示，在诱导骨髓祖细胞凋亡的同时，TNF-α通过激活强大且特异性的p65-核因子κB（NF-κB）依赖性基因程序来促进HSC存活和骨髓分化。该程序主要阻止坏死性死亡而不是细胞凋亡，诱导免疫调节功能，并将HSC用于骨髓细胞生产。这些TNF-α驱动的机制对HSC对炎症应激的应答至关重要，但也在老年和恶性HSC中被劫持。研究结果揭示了几种TNF-α介导的HSC独特的促存活机制，突出了坏死作用在HSC杀伤中的重要作用，并确立了TNF-α是HSC的主要促存活和促再生因子。

据了解，炎症通过受损细胞的清除和干细胞活化来协调组织再生。HSC在炎症应激下存活，可以杀死其他血细胞，但这种作用背后的机制仍然知之甚少。

附：英文原文

Title: TNF-α Coordinates Hematopoietic Stem Cell Survival and Myeloid Regeneration

Author: Masayuki Yamashita, Emmanuelle Passegué

Issue&Volume: Volume 25 Issue 3

Abstract: Inflammation coordinates tissue regeneration via damaged cell removal and stem cell activation. Hematopoietic stem cells (HSCs) survive inflammatory stress that kills other blood cells, but the mechanisms underlying this effect remain poorly understood. Here, we find that tumor necrosis factor α (TNF-α) acts differently on HSCs and progenitors, thus facilitating hematopoietic clearance and promoting regeneration. We show that while inducing myeloid progenitor apoptosis, TNF-α promotes HSC survival and myeloid differentiation by activating a strong and specific p65-nuclear factor κB (NF-κB)-dependent gene program that primarily prevents necroptosis rather than apoptosis, induces immunomodulatory functions, and poises HSCs for myeloid cell production. These TNF-α-driven mechanisms are critical for HSC response to inflammatory stress but are also hijacked in aged and malignant HSCs. Our results reveal several TNF-α-mediated pro-survival mechanisms unique to HSCs, highlight an important role for necroptosis in HSC killing, and establish TNF-α as a major pro-survival and pro-regeneration factor for HSCs.

DOI: 10.1016/j.stem.2019.05.019

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30223-1