Characterization of naked mole‐rat hematopoiesis reveals unique stem and progenitor cell patterns and neotenic traits

Abstract

Naked mole rats (NMRs) are the longest-lived rodents yet their stem cell characteristics remain enigmatic. Here, we comprehensively mapped the NMR hematopoietic landscape and identified unique features likely contributing to longevity. Adult NMRs form red blood cells in spleen and marrow, which comprise a myeloid bias toward granulopoiesis together with decreased B-lymphopoiesis. Remarkably, youthful blood and marrow singlecell transcriptomes and cell compositions are largely maintained until at least middle age. Similar to primates, the primitive stem and progenitor cell (HSPC) compartment is marked by CD34 and THY1. Stem cell polarity is seen for Tubulin but not CDC42, and is not lost until 12 years of age. HSPC respiration rates are as low as in purified human stem cells, in concert with a strong expression signature for fatty acid metabolism. The pool of quiescent stem cells is higher than in mice, and the cell cycle of hematopoietic cells is prolonged. By characterizing the NMR hematopoietic landscape, we identified resilience phenotypes such as an increased quiescent HSPC compartment, absence of age-related decline, and neotenic traits likely geared toward longevity.

Living a longer life: unique lessons from the naked mole‐rat blood system

“…In conclusion, the use of alternative models to study ageing holds great potential for the ageing field, and this study by Emmrich et al (2022) has not only provided the research community with a set of useful research tools, but it has also revealed exciting insights into unique strategies to maintain a healthy immune system with ageing and ultimately possibly achieve a longer life (Fig 1).…”

“…In this issue of EMBO Journal, (Emmrich et al, 2022) explore the haematopoietic system of the naked mole-rat (NMR), a uniquely long-lived rodent, and report interesting evolutionary adaptations that might contribute to the longevity of this species.…”

“…Targeting the dysfunctions in the aged haematopoietic system has the potential to increase human health and lifespan, and direct interventions that ameliorate the ageing effects on HSCs hold great potential in this direction. In this issue of EMBO Journal , (Emmrich et al, 2022 ) explore the haematopoietic system of the naked mole‐rat (NMR), a uniquely long‐lived rodent, and report interesting evolutionary adaptations that might contribute to the longevity of this species.…”

“…While the mouse model system offers many advantages, the use of other models can widen our understanding of ageing of the haematopoietic system and provide researchers with novel tools to target ageing in humans. Emmrich et al ( 2022 ) here present an elegant in‐depth characterisation of the haematopoietic system of the NMR and offer a set of useful tools in the form of species cross‐reactive antibodies for flow cytometric analysis, as well as a single‐cell transcriptomic profiling database easily accessible using a dedicated online interface. Emmrich et al ( 2022 ) also uncover several novel features of NMR haematopoietic system that might have evolved to support their exceptionally long life (Fig 1 ).…”

“…Emmrich et al ( 2022 ) here present an elegant in‐depth characterisation of the haematopoietic system of the NMR and offer a set of useful tools in the form of species cross‐reactive antibodies for flow cytometric analysis, as well as a single‐cell transcriptomic profiling database easily accessible using a dedicated online interface. Emmrich et al ( 2022 ) also uncover several novel features of NMR haematopoietic system that might have evolved to support their exceptionally long life (Fig 1 ). One of the striking examples in that respect is the fact that NMRs suffer no age‐associated changes in the cell frequencies between different immune cell subtypes at least until middle age, a phenomenon that is evident in both mice and humans.…”