Aging of hematopoietic stem cells (HSCs) is associated with a decline in their regenerative capacity and multi-lineage 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 (ADRβ3) signaling in the bone marrow microenvironment of young mice led to premature HSC aging, as evidenced by appearance of HSC phenotypes reminiscent of physiological aging. Strikingly, supplementation of a sympathomimetic acting selectively on ADRβ3 to old mice significantly rejuvenated the in vivo function of aged HSCs, suggesting that the preservation or restitution of bone marrow SNS innervation during aging may hold the potential for new HSC rejuvenation strategies.

Aging of hematopoietic stem cells (HSCs) is associated with a decline in their regenerative capacity and multi-lineage 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 (ADRβ3) signaling in the bone marrow microenvironment of young mice led to premature HSC aging, as evidenced by appearance of HSC phenotypes reminiscent of physiological aging. Strikingly, supplementation of a sympathomimetic acting selectively on ADRβ3 to old mice significantly rejuvenated the in vivo function of aged HSCs, suggesting that the preservation or restitution of bone marrow SNS innervation during aging may hold the potential for new HSC rejuvenation strategies.Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Sentiment evolution is a key component of interactions in blended learning. Although interactions have attracted considerable attention in online learning contexts, there is scant research on examining sentiment evolution over different interactions in blended learning environments. Thus, in this study, sentiment evolution at different interaction levels was investigated from the longitudinal data of five learning stages of 38 postgraduate students in a blended learning course. Specifically, text mining techniques were employed to mine the sentiments in different interactions, and then epistemic network analysis (ENA) was used to uncover sentiment changes in the five learning stages of blended learning. The findings suggested that negative sentiments were moderately associated with several other sentiments such as joking, confused, and neutral sentiments in blended learning contexts. Particularly in relation to deep interactions, student sentiments might change from negative to insightful ones. In contrast, the sentiment network built from social-emotion interactions shows stronger connections in joking-positive and joking-negative sentiments than the other two interaction levels. Most notably, the changes of co-occurrence sentiment reveal the three periods in a blended learning process, namely initial, collision and sublimation, and stable periods. The results in this study revealed that students’ sentiments evolved from positive to confused/negative to insightful.

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