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Straight, M. E.

Publications and source records attributed to Straight, M. E..

2 recordsLinked to original sources

Naked mole-rat hematopoietic stem and progenitors are highly quiescent with an inherent myeloid bias

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 is a neotenic trait. A myeloid bias towards granulopoiesis in concert with decreased B-lymphopoiesis defines the marrow composition, resembling fetal leukopoiesis. Very similar to primates, the primitive stem cell compartment is marked by CD34 and THY1. Remarkably, stem and progenitor respiration rates are as low as in human cells, while NMR cells show 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. Our work provides a platform to study immunology and stem cell biology in an animal model of exceptional longevity. TeaserJuvenile features of hematopoiesis shape the blood system of the longest-lived rodent.

cell biology↗

The hematopoietic landscape at single-cell resolution reveals unexpected stem cell features in naked mole-rats

Naked mole-rats are the longest-lived rodents endowed with resistance to cancer and age-related diseases, yet their stem cell characteristics remain enigmatic. We profiled the naked mole-rat hematopoietic system down to single-cell resolution, and identified several unique features likely contributing to longevity. In adult naked mole-rats red blood cells are formed in spleen and marrow, a neotenic feature beneficial for hypoxic environments and to prevent anemia. Platelet numbers are lower compared to short-lived mice, which may preclude age-related platelet increase and thrombosis. T cells mature in thymus and lymph nodes, providing a supply of T cells after age-related thymus involution. The pool of quiescent stem cells is higher than in mice, and HSCs overexpress an oxidative phosphorylation signature, revealing a new paradigm of stem cell metabolism to benefit longevity and oppose oncogenesis. Our work provides a platform to study immunology and stem cell biology in an animal model of healthy aging. HIGHLIGHTSO_LIFlow cytometry labelling panel to purify viable naked mole-rat HSPCs C_LIO_LIThe spleen as the major site of erythropoiesis in the naked mole-rat C_LIO_LINaked mole-rats show extrathymic T-cell development under homeostatic conditions C_LIO_LINaked mole-rat hematopoietic stem cells (HSCs) have high OXPHOS activity C_LI

immunology↗