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bioRxiv · 10.1101/859454

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

Emmrich, S.·Mariotti, M.·Takasugi, M.·Straight, M. E.·Trapp, A.·Gladyshev, V. N.·Seluanov, A.·Gorbunova, V.

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Abstract

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

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Emmrich, S., Mariotti, M., Takasugi, M., Straight, M. E., Trapp, A., Gladyshev, V. N., Seluanov, A., Gorbunova, V.. 2019-11-29. The hematopoietic landscape at single-cell resolution reveals unexpected stem cell features in naked mole-rats. https://doi.org/10.1101/859454

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