Cell Discovery:头发为什么会变白?单细胞转录组测序揭示原因并找到干预靶点

2022-05-28 王聪 “生物世界”公众号

人的头发变白通常是一个从中年开始的渐进过程。衰老相关的头发变白与黑色素细胞和黑色素细胞干细胞(MeSC)的耗竭有关,这可能受到头皮微环境中氧化应激和神经内分泌信号等因素的影响。

脱发、白发等头发状况,是人类遇到的最普遍的状况之一。但由于人类毛囊(hair follicle,HF)在疾病和健康中的作用尚不清楚,因此它们通常没有得到有效控制。

人的头发变白通常是一个从中年开始的渐进过程。衰老相关的头发变白与黑色素细胞和黑色素细胞干细胞(MeSC)的耗竭有关,这可能受到头皮微环境中氧化应激和神经内分泌信号等因素的影响。

值得注意的是,在同龄人中,白发的生长速度和生物物理特性与有色发不同,这表明它们的毛囊上皮谱系发生了变化。这与在小鼠中的发现一致,毛囊中的上皮干细胞为黑色素细胞干细胞(MeSC)提供了功能生态位(niche)并指导了它们的分化。那么,人类的头发在变白的过程中,除了黑色素细胞的耗竭,还与那些细胞有关?能否通过药物干预这一过程?

2022年5月24日,中科院上海营养与健康研究所张亮研究员、汪思佳研究员、上海交通大学医学院附属第九人民医院李青峰主任医师作为共同通讯作者,在 Cell Discovery 期刊发表了题为:Single-cell transcriptomics reveals lineage trajectory of human scalp hair follicle and informs mechanisms of hair graying 的研究论文。

该研究通过单细胞转录组测序,以前所未有的细节揭示了人头皮毛囊(hsHF)的谱系轨迹,并揭示了在小鼠毛囊中未发现的多个意想不到的特征。该研究还证明除了黑色素细胞耗竭外,人类头发变白的早期阶段也与基质毛发祖细胞的特定耗竭有关,与毛囊干细胞无关。

此外,该研究还发现,毛发祖细胞的耗竭伴随着它们的 P53 通路激活,通过 P53 抑制剂(PFT-α)阻断可以改善小鼠头发变白的情况,这为头发变白这一普遍的头发状况开辟了一个有希望的治疗途径。

研究团队收集了整形手术中废弃的人类头部皮肤样本,分别来自18岁(F18,主要是黑发)、31岁(F31,灰白头发)、59岁(F59,主要是黑发)、62岁(F62,灰白头发)的女性。

然后,对 F18 和 F59 这两个黑发样本的人头皮毛囊直接进行单细胞转录组测序,而对于 F31 和 F62 这两个灰白头发样本,则将其进一步分为黑发人头皮毛囊(F31B、F62B)和白发人头皮毛囊(F31W、F62W),并分别进行单细胞转录组测序。

研究团队通过这些样本的单细胞转录组测序结果得到了头发变白早期阶段的简明单细胞图谱,还以前所未有的细节揭示了人头皮毛囊(hsHF)的谱系轨迹,并揭示了在小鼠毛囊中未曾发现的多个意想不到的特征,例如毛囊生长阶段存在内凸状隔层,缺乏离散的伴生层,以及毛囊干细胞中富集的上皮间质转化特征。

人类头发变白可归因于黑色素细胞耗竭,但尚不清楚该过程是否还涉及毛囊上皮谱系改变。为了解决这一问题,研究团队对上述样本中来自同一人的相邻的黑发人头皮毛囊和白发人头皮毛囊进行了对比。正如预期的那样,白发人头皮毛囊比黑发人头皮毛囊的黑色素细胞要少得多。但除了黑色素细胞外,他们发现,人类头发变白早期阶段也与基质毛发祖细胞的特定消耗有关,而与毛囊干细胞无关。

该研究还进一步发现,毛发祖细胞的耗竭伴随着它们的 P53 通路激活,而通过 P53 抑制剂(PFT-α)阻断 P53,则可以改善小鼠电离辐射诱导的头发变白,为这种普遍的头发状况开辟了一条有希望的治疗途径。

原始出处:

Wu, S., Yu, Y., Liu, C. et al. Single-cell transcriptomics reveals lineage trajectory of human scalp hair follicle and informs mechanisms of hair graying. Cell Discov 8, 49 (2022). https://doi.org/10.1038/s41421-022-00394-2

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    2022-10-20 yahu
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    2022-08-13 mjldent
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    2022-06-15 柳叶一刀
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    2022-05-28 qindq
  9. [GetPortalCommentsPageByObjectIdResponse(id=1872439, encodeId=961118e24394c, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sat Apr 29 05:48:15 CST 2023, time=2023-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1926561, encodeId=839119265611f, content=<a href='/topic/show?id=77f5933e465' target=_blank style='color:#2F92EE;'>#转录组测序#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93374, encryptionId=77f5933e465, topicName=转录组测序)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f5e185, createdName=zlawrance, createdTime=Sat Apr 22 10:48:15 CST 2023, time=2023-04-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2013881, encodeId=1ddb2013881c6, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Thu Mar 09 06:48:15 CST 2023, time=2023-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1783736, encodeId=c1321e83736e2, content=<a href='/topic/show?id=d195513038' target=_blank style='color:#2F92EE;'>#cover#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5130, encryptionId=d195513038, topicName=cover)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=52c7237, createdName=yahu, createdTime=Thu Oct 20 05:48:15 CST 2022, time=2022-10-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1747456, encodeId=82a21e47456bc, content=<a href='/topic/show?id=832e93345c3' target=_blank style='color:#2F92EE;'>#转录#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93345, encryptionId=832e93345c3, topicName=转录)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=58df35929710, createdName=mjldent, createdTime=Sat Aug 13 17:48:15 CST 2022, time=2022-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962765, encodeId=f09d1962e65f0, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Wed Jun 15 01:48:15 CST 2022, time=2022-06-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1420231, encodeId=d1c61420231e6, content=<a href='/topic/show?id=5f3a9336904' target=_blank style='color:#2F92EE;'>#转录组#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93369, encryptionId=5f3a9336904, topicName=转录组)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2c9e3571203, createdName=marlenexl, createdTime=Sat May 28 06:48:15 CST 2022, time=2022-05-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1468618, encodeId=0c9b146861805, content=<a href='/topic/show?id=7f7f443337a' target=_blank style='color:#2F92EE;'>#头发#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44333, encryptionId=7f7f443337a, topicName=头发)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f09e6924959, createdName=qindq, createdTime=Sat May 28 06:48:15 CST 2022, time=2022-05-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1587946, encodeId=5533158e94639, content=<a href='/topic/show?id=cb1e1006ebd' target=_blank style='color:#2F92EE;'>#ISC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10067, encryptionId=cb1e1006ebd, topicName=ISC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=173417575755, createdName=yankaienglish, createdTime=Sat May 28 06:48:15 CST 2022, time=2022-05-28, status=1, ipAttribution=)]
    2022-05-28 yankaienglish

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