Environmental Impact on HSC Aging

One of the most important recent research outputs from the group is likely the 2022 manuscript detailing the role that inflammation and infection can play upon hematopoietic aging, which was published in the journal Cell Stem Cell [1]. This manuscript makes the important observation that HSCs never recover their functional potency following acute challenge with inflammation or infection, which is distinct from the concept of inflammaging, which requires ongoing low-level inflammation to sustain its inhibitory effects on cell biology. Our work suggests a model where sequential exposures to such agonists, even if separated by several months or even years, can have an attritional effect on the HSC pool that accumulates across the lifetime of the organism and acts as a driver of the process of aging. This fundamentally contradicts the established concept that HSCs possess extensive self-renewal potential. We have also contributed to a number of other published studies that have investigated different aspects of the interaction between HSCs and inflammatory/infection stimuli during emergency hematopoiesis. These include: the induction of emergency megakaryopoiesis following infection with Influenza A virus [2]; an unexpected role for HSCs as antigen-presenting cells that may restrict the outgrowth of pre-malignant clones [3]; and the finding that the immune hypersensitivity response has a negligible effect on HSC function [4]. In addition, we have further explored the phenomenon of HSC dormancy, resulting in collaborative publications showing that: maintenance of HSC dormancy prevents the development of an aged state [5]; and that conventional label retention systems underestimate the frequency of dormant HSCs [6].

1. Bogeska et al., Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging. Cell Stem Cell 29(8):1273-1284 (2022)
2. Rommel et al., Influenza A virus infection instructs hematopoiesis to megakaryocyte-lineage output. Cell Rep. 41(1):111447 (2022)
3. Hernández-Malmierca et al., Antigen presentation safeguards the integrity of the hematopoietic stem cell pool. Cell Stem Cell 29(5):760-775 (2022)
4. Bujanova et al., Hypersensitivity response has negligible impact on hematopoietic stem cells. Cell Rep. 16(8):1884-1893 (2021)
5. Saçma et al., Haematopoietic stem cells in perisinusoidal niches are protected from ageing. Nat. Cell Biol. 21(11):1309-1320 (2019)
6. Morcos et al., Continuous mitotic activity of primitive hematopoietic stem cells in adult mice. J. Exp. Med. 217(6):e20191284 (2020)