Transcriptomics,Genomics

Dataset Information

158

Loss of adrenergic nerves in bone marrow drives hematopoietic stem cell niche aging


ABSTRACT: Aging of hematopoietic stem cells (HSCs) is associated with the decline of their regenerative capacity, and multi-lineage differentiation potential, contributing to development of blood disorders. The bone marrow microenvironment was recently suggested to influence HSC aging, however the underlying mechanisms remain largely unknown. Here, we show that HSC aging critically depends on bone marrow innervation by the sympathetic nervous system (SNS), as premature loss of SNS nerves or adrenoreceptor b3 (ADRb3) signaling in the microenvironment accelerated the appearance of HSC aging phenotypes reminiscent of physiological aging. Strikingly, supplementation of ADRb3 sympathomimetics to old mice significantly rejuvenated in vivo function of old HSCs, suggesting that the preservation or restitution of SNS innervation during aging may hold the potential for novel HSC rejuvenation strategies. Overall design: mRNA profiles of sorted bone marrow hematopoietic stem cells were generated from saline treated young and old and BRL37344 treated old mice in triplicates by Illumina NextSeq500 sequencing

INSTRUMENT(S): Illumina NextSeq 500 (Mus musculus)

SUBMITTER: Paul Frenette 

PROVIDER: GSE109546 | GEO | 2018-05-01

REPOSITORIES: GEO

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Publications

Adrenergic nerve degeneration in bone marrow drives aging of the hematopoietic stem cell niche.

Maryanovich Maria M   Zahalka Ali H AH   Pierce Halley H   Pinho Sandra S   Nakahara Fumio F   Asada Noboru N   Wei Qiaozhi Q   Wang Xizhe X   Ciero Paul P   Xu Jianing J   Leftin Avigdor A   Frenette Paul S PS  

Nature medicine 20180507 6


Aging of hematopoietic stem cells (HSCs) is associated with a decline in their regenerative capacity and multilineage differentiation potential, contributing to the development of blood disorders. The bone marrow microenvironment has recently been suggested to influence HSC aging, but the underlying mechanisms remain largely unknown. Here we show that HSC aging critically depends on bone marrow innervation by the sympathetic nervous system (SNS), as loss of SNS nerves or adrenoreceptor β3 signal  ...[more]

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