小柯机器人

美国爱因斯坦医学院Paul S. Frenette研究团队发现，伤害性感受神经元能够调节造血干细胞动员。相关论文于2020年12月23日在线发表于国际学术期刊《自然》。

据研究人员介绍，造血干细胞（HSC）驻留在骨髓的特殊微环境（通常称为“niches”）中，这是受多种细胞成分（包括神经）影响的复杂环境。尽管已知交感神经调节HSC的微环境，但伤害性神经元在骨髓中的作用仍不清楚。

研究人员发现，强制的HSC动员需要伤害感受神经，并且它们与交感神经协作以在骨髓中维持HSC。伤害感受性神经元通过降钙素基因相关肽（CGRP）的分泌来驱动粒细胞集落刺激因子（G-CSF）诱导的HSC动员。

不同于交感神经，它通过微环境间接调节HSC，而CGRP通过受体活性修饰蛋白1（RAMP1）和降钙素受体样受体（CALCRL）直接作用于HSC，从而通过激活Gαs/腺苷酸环化酶/cAMP途径来促进分泌。

摄入含有辣椒素的食物（辣椒素是辣椒的天然成分，可以触发伤害性神经元的活化），可显著增强小鼠的HSC动员能力。因此，靶向伤害性神经系统可能是一种提高HSC产量的策略。

附：英文原文

Title: Nociceptive nerves regulate haematopoietic stem cell mobilization

Author: Xin Gao, Dachuan Zhang, Chunliang Xu, Huihui Li, Kathleen M. Caron, Paul S. Frenette

Issue&Volume: 2020-12-23

Abstract: Haematopoietic stem cells (HSCs) reside in specialized microenvironments in the bone marrow—often referred to as ‘niches’—that represent complex regulatory milieux influenced by multiple cellular constituents, including nerves1,2. Although sympathetic nerves are known to regulate the HSC niche3,4,5,6, the contribution of nociceptive neurons in the bone marrow remains unclear. Here we show that nociceptive nerves are required for enforced HSC mobilization and that they collaborate with sympathetic nerves to maintain HSCs in the bone marrow. Nociceptor neurons drive granulocyte colony-stimulating factor (G-CSF)-induced HSC mobilization via the secretion of calcitonin gene-related peptide (CGRP). Unlike sympathetic nerves, which regulate HSCs indirectly via the niche3,4,6, CGRP acts directly on HSCs via receptor activity modifying protein 1 (RAMP1) and the calcitonin receptor-like receptor (CALCRL) to promote egress by activating the Gαs/adenylyl cyclase/cAMP pathway. The ingestion of food containing capsaicin—a natural component of chili peppers that can trigger the activation of nociceptive neurons—significantly enhanced HSC mobilization in mice. Targeting the nociceptive nervous system could therefore represent a strategy to improve the yield of HSCs for stem cell-based therapeutic agents.

DOI: 10.1038/s41586-020-03057-y

Source: https://www.nature.com/articles/s41586-020-03057-y

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