加拿大多伦多大学Stephanie Z. Xie小组宣布他们的最新研究探明了人类造血干细胞记得炎症应激。相关论文于2026年5月27日发表于国际顶尖学术期刊《自然》杂志上。

为了从经验上理解这种适应，课题组建立了异种移植炎症恢复模型，并对异种移植的人类造血干细胞进行了单细胞多组学研究。两种转录和表观遗传学上不同的HSC亚群被鉴定为其中一种，称为HSC炎症记忆（HSC- iM），保留了先前炎症治疗的分子记忆。HSC-iM亚群表现出静止和抑制的造血输出。从分子上讲，HSC-iM程序在成人和儿童样本中的HSC中富集，包括COVID-19恢复，镰状细胞病，衰老和克隆造血，建立了其异种移植模型的有效性和HSC-iM的生理相关性。HSC- iM的克隆造血突变通过促进HSC的激活和分化来减轻炎症应激的影响。

此外，在异种移植物和生理环境中，证实了促炎HSC-iM转录程序向分化的免疫后代的传递。最后，在人群队列分析中，循环血细胞中HSC- iM程序的富集与全因死亡率的高风险评分相关，强调了这一新发现的HSC亚群在一生中表征异质健康结局方面的临床相关性。

据悉，炎症激活血细胞，导致衰老和恶性肿瘤。造血干细胞（HSCs）可以在感染的一生中存活，从而维持终身的造血功能，但人类HSCs如何应对和适应炎症应激在很大程度上是未知的。

附：英文原文

Title: Human haematopoietic stem cells remember inflammatory stress

Author: Zeng, Andy G. X., Nagree, Murtaza S., Jakobsen, Niels Asger, Shah, Sayyam, Varesi, Angelica, Kang, Jasmine Ryu Won, Murison, Alex, Cheong, Jin-Gyu, Turkalj, Sven, Zhang, Xuan, Radtke, Felix A., Abera, Tsega-Ab, Lim, Isabel N. X., Jin, Liqing, Arajo, Joana, Aguilar-Navarro, Alicia G., Parris, Darrien, McLeod, Jessica, Kim, Hyerin, Lee, Ho Seok, Zhang, Lin, Boulanger, Mason, Bader, Elyssa, Gbeha, Elias, Parkhurst, Christopher N., Wagenblast, Elvin, Flores-Figueroa, Eugenia, Wang, Bo, Schwartz, Gregory W., Shultz, Leonard D., Nam, Anna S., Grimes, H. Leighton, Josefowicz, Steven Z., Awadalla, Philip, Vyas, Paresh, Dick, John E., Xie, Stephanie Z.

Issue&Volume: 2026-05-27

Abstract: Inflammation activates blood cells, contributing to ageing and malignancy1,2,3. Haematopoietic stem cells (HSCs) survive a lifetime of infection to sustain life-long haematopoiesis1,2,3,4,5,6,7,8,9, but how human HSCs respond and adapt to inflammatory stress is largely unknown. Here, to empirically understand this adaptation, we developed xenograft inflammation–recovery models and performed single-cell multiomics on xenografted human HSCs. Two transcriptionally and epigenetically distinct HSC subsets were identified with one, termed HSC inflammatory memory (HSC-iM), retaining a molecular memory of previous inflammatory treatments. The HSC-iM subset exhibited quiescence and restrained haematopoietic output. Molecularly, the HSC-iM program was enriched in HSCs from adult and paediatric samples across conditions ranging from COVID-19 recovery, sickle cell disease, ageing and clonal haematopoiesis, establishing both the validity of our xenograft models and the physiological relevance of HSC-iM. Clonal haematopoiesis mutations in HSC-iM attenuated the effects of inflammatory stress by promoting HSC activation and differentiation. Moreover, transmission of the pro-inflammatory HSC-iM transcriptional program to differentiated immune progeny was demonstrated in xenograft and physiological settings. Finally, HSC-iM program enrichment in circulating blood cells was associated with a heightened risk score for all-cause mortality in population cohort analyses, underscoring the clinical relevance of this newly identified HSC subset in characterizing heterogeneous health outcomes across a lifetime.

DOI: 10.1038/s41586-026-10522-7

Source: https://www.nature.com/articles/s41586-026-10522-7