神奇!Nature:吃辣竟可动员你的造血干细胞,或有助于治疗血液疾病

2021-01-08 侯媛媛 生物探索

造血干细胞(HSC)是血液系统中的成体干细胞,常见于骨髓、外周血及脐带血。在人的一生中,HSC需要根据机体的生理需求适时的补充血液系统各个成熟细胞组分。

造血干细胞(HSC)是血液系统中的成体干细胞,常见于骨髓、外周血及脐带血。在人的一生中,HSC需要根据机体的生理需求适时的补充血液系统各个成熟细胞组分,例如在损伤、炎症等应激状态下,它需要调节和维持体内血液系统各个细胞组分的生理平衡。因为HSC具有分化成各类血细胞的潜能,因而成为治疗血液系统疾病和自身免疫疾病的首选。然而,动员HSC的详细机制仍然未知。

近日,来自阿尔伯特爱因斯坦医学院的研究人员在《Nature》上发表题为Nociceptive nerves regulate haematopoietic stem cell mobilization的文章,发现伤害性神经可动员造血干细胞,这为干细胞移植及血液疾病治疗提供新方向。

先前有研究表明,HSC的动员受神经调控。因此,研究人员首先通过免疫荧光成像技术调查了小鼠骨髓中的总神经密度,发现伤害性神经和交感神经均有投射,且伤害性神经占比高达77%。

为进一步确定两种神经的作用机制,研究人员单独切断其中一种神经,发现对骨髓中在的HSC数量并没有影响,但同时切断两种,HSC的数量却明显减少。在减少时,持续增加降钙素基因相关肽CGRP(伤害性神经元分泌的神经递质)或β-肾上腺素能受体激动剂(交感神经元分泌的神经递质),可恢复HSC数量。这表明伤害性神经和交感神经共同形成神经闭环网络,控制HSC的形成。

伤害性神经元促进HSC动员

已有研究证实,G-CSF(粒细胞集落刺激因子)可动员HSC从骨髓进入血液。实验人员在切断伤害性神经后发现,HSC数量虽不受影响,但HSC的动员迁移能力却减弱。这表明缺乏伤害性神经元会选择性地影响HSC的流出,并需要伤害性神经元才能使驱动力强的G-CSF诱导的HSC从骨髓进入血液。

接下来,研究人员探究了CGRP在HSC动员中的作用。发现CGRP治疗可显著增加G-CSF动员的HSC数量,这表明G-CSF诱导的HSC动员受伤害性神经衍生的神经肽CGRP调控。进一步探究CGRP促进HSC流出过程,发现由CALCRL和RAMP1组成的CGRP受体,这表明CGRP通过其异源二聚体受体RAMP1-CALCRL作用于造血细胞,从而促进HSC流出。

CGRP通过同源受体RAMP1-CALCRL诱导HSC动员



伤害性神经元介导HSC动员的信号通路图

伤害性神经在HSC动员中的积极作用使研究人员大胆推测,辛辣食物的摄入可能触发骨髓中的HSC动员(辛辣食物的摄入会触发伤害性神经元活化)。随后,研究人员给小鼠喂食了含有辣椒素的饮食,结果显示食用辛辣食物的小鼠中G-CSF诱导的HSC数量显着高于普通食物喂养的小鼠。

含辣椒素饮食对小鼠HSC动员的影响

此外,研究人员在文章的最后论述到,如果一个人每天吃10个墨西哥红辣椒,连吃4天,是有可能动员体内造血干细胞的。

原始出处:

Xin Gao  1   2 , Dachuan Zhang  1   2 , Chunliang Xu  1   2 , et al.Nociceptive nerves regulate haematopoietic stem cell mobilization.Nature .2020 Dec 23.doi: 10.1038/s41586-020-03057-y. Online ahead of print. 

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    2021-11-26 liye789132251
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    2021-03-09 ms8000000693681640

    学习了

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    2021-01-12 ms7000000737941079

    学到了

    0

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    2021-01-11 独孤立克

    干细胞是热点,但是进入临床仍然需要时间和临床疗效验证哦

    0

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    2021-01-10 俅侠
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    2021-01-10 hywen7332
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    2021-01-08 zb1235672

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造血干细胞(HSC)驻留在骨髓(BM)干细胞壁龛中,这里HSC调节信号的重要来源。放疗和化疗会破坏了HSC的微环境,包括其窦状血管和血管周细胞,导致造血功能恢复迟缓。

Blood:UTX通过调节衰老相关基因表达维持造血稳态

表观遗传调控对造血系统的维持至关重要,而表观遗传调控一旦失控就有可能导致造血系统紊乱。在该研究中,研究人员发现UTX通过全局调控衰老相关基因在造血系统中发挥重要作用。

Blood:c-Myc单倍体剂量不足在HSC维持中的作用

近日,《血液》杂志上发表了一篇新研究,报道了c-Myc对造血作用的剂量效应及其在造血干细胞(HSC)和骨髓壁龛细胞中介导Wnt/b-catenin通路的独特作用。