Nature:重磅!两篇论文共同揭示:新型肺细胞

2018-08-07 探索菌 生物探索

8月1日,《Nature》连发两篇文章,同时揭示了一种新型肺细胞——“肺部离子细胞”(pulmonary ionocyte)。两个不同的研究团队利用单细胞RNA测序技术对人类以及小鼠的呼吸道细胞绘制了详细的分子图谱,从中发现了新的知识点。

8月1日,《Nature》连发两篇文章,同时揭示了一种新型肺细胞——“肺部离子细胞”(pulmonary ionocyte)。两个不同的研究团队利用单细胞RNA测序技术对人类以及小鼠的呼吸道细胞绘制了详细的分子图谱,从中发现了新的知识点。


肺部离子细胞(橙色)通过邻近的上皮细胞(细胞核,青色)延伸至呼吸上皮层。这一新发现的细胞类型会高度表达CFTR,一种突变时与囊性纤维化有关的基因。(图片来源:ANNA HUPALOWSKA, DANIEL MONTORO)

这两份围绕“呼吸上皮细胞”的最新研究揭示了数千个肺细胞的基因表达模式,从中挖掘出一种前所未知的新型肺细胞,即肺部离子细胞。更重要的是,这一新细胞会高度表达一种与囊性纤维化有关的突变基因——囊性纤维跨膜转导调控因子CFTR(cystic fibrosis transmembrane conductance regulator)。

囊性纤维化是一种遗传性外分泌腺疾病,主要影响胃肠道和呼吸系统。CFTR缺乏和缺陷容易导致粘液增厚、气道堵塞和反复感染

01.论文一

A revised airway epithelial hierarchy includes CFTR-expressing ionocytes

哈佛大学医学院附属麻省总医院(MGH)的肺内科医生Jayaraj Rajagopal一直在研究肺再生,并希望通过单细胞测序分析肺干细胞群的差异。他和Broad研究所的计算生物学家Aviv Regev团队合作,共同鉴定了成年小鼠器官中数千个上皮细胞的转录图谱。

研究团队分析了两种最常见的细胞类型:分泌细胞(club cells),分泌呼吸道粘液成分,包括抗菌分子以及免疫调控蛋白;纤毛细胞(ciliated cells),携带一种叫做纤毛的突出结构,负责清除粘液和碎片垃圾。此外,他们还分析了一些罕见、不常见的细胞类型,包括产生粘液蛋白的杯状细胞(goblet cells)、扮演免疫传感器的簇状细胞(tuft cells)、感知氧气水平和传递信号的神经内分泌细胞(neuroendocrine cells)。

结果显示,上皮细胞下层的基底细胞(basal cells)不仅仅直接生成分泌细胞,还会生成除了杯状细胞以外的所有罕见细胞。他们发现,有几组呼吸道细胞基因表达模式存在前所未知的基因表达差异,以及发现肺部新的结构和细胞分化的新途径。他们还揭示了几种新的细胞类型,并将其中一种命名为“肺部离子细胞”(pulmonary ionocyte)。



他们发现,这些肺部新细胞的基因表达模式类似于鱼类和两栖类的离子细胞,包括转录因子Foxi1的编码基因。在鱼类中,离子细胞通常负责调控动物组织与周围水环境之间的钠、氯和钙离子交换,从而维持体液溶质浓度平衡。目前还不清楚在哺乳动物呼吸道中,肺离子细胞是否具有类似功能,即便细胞确实表达有多种离子运输基因。

更重要的是,研究团队发现,肺部离子细胞高度表达CFTR,而且是CFTR主要的来源。CFTR是一种有助于调控液体运输和粘液浓度的膜蛋白。在小鼠和人类肺模型中,这类细胞可能在囊性纤维化中发挥作用。

“我们发现了很多改写肺部生物学的新知识点。” Rajagopal总结道。

02.论文二

A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte

另一项研究由诺华公司的生物学家Aron Jaffe和哈佛大学系统生物学家Allon Klein合作完成。Allon Klein之前已经开发了一种单细胞RNA测序方法,Aron Jaffe将其描述为“一种完美的技术,可以在呼吸道上对各种上皮细胞进行全面的观察和分析”。

他们对人类支气管上皮细胞和小鼠气管上皮细胞进行RNA测序。同样,他们也发现了肺部离子细胞,以及在熟悉的细胞中发现新的基因表达模式。为了更好地了解离子细胞在囊性纤维化中可能的作用,研究团队比较了人类和小鼠离子细胞中CFTR的表达模式。与其他研究结果一致的是,研究人员发现,肺离子细胞是人类和小鼠呼吸道中CFTR蛋白的主要来源。

“发现这一新型的罕见细胞类型,确实令人惊讶。CFTR已经被研究了很长一段时间,被认为在许多呼吸道细胞中广泛表达。但是现在的结果表明,上皮细胞比之前认为的要复杂得多。” Jaffe强调道。

03.下一步

现在,研究团队已经表明转录因子Foxi1是这些离子细胞转录程序的核心。下一步问题是:Foxi1是直接与CFTR基因相互作用,还是通过其他转录因子或其他蛋白调控CFTR基因表达?

除了研究离子细胞在肺功能中的潜在作用外,研究人员认为还可以进一步分析最新数据,特别是关于转录因子和细胞表面标记的编码基因的表达细节。

原始出处:

[1]Daniel T. Montoro, Adam L. Haber, Moshe Biton, et al. A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature. 2018 Aug 1.

[2]Plasschaert LW, Zilionis R, Choo-Wing R, et al. A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte. Nature. 2018 Aug 1.

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    2018-11-24 liye789132251
  2. [GetPortalCommentsPageByObjectIdResponse(id=1883227, encodeId=ff2b188322ebb, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Nov 24 19:31:00 CST 2018, time=2018-11-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1663440, encodeId=14d51663440ca, content=<a href='/topic/show?id=c8f982280c2' target=_blank style='color:#2F92EE;'>#肺细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82280, encryptionId=c8f982280c2, topicName=肺细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=765025615163, createdName=thinkibmz_44722602, createdTime=Mon Apr 29 23:31:00 CST 2019, time=2019-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=337660, encodeId=734e33e66085, content=好厉害,内科学,解剖学,各种课本要改版了, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d7e71713450, createdName=太阳系小猪, createdTime=Fri Aug 10 07:20:55 CST 2018, time=2018-08-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1549356, encodeId=3ee015493562d, content=<a href='/topic/show?id=f7879600061' target=_blank style='color:#2F92EE;'>#重磅#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96000, encryptionId=f7879600061, topicName=重磅)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3acc14121561, createdName=xxxx1054, createdTime=Thu Aug 09 02:31:00 CST 2018, time=2018-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=337331, encodeId=c8e033e33112, content=真理的唯一需要不断探索, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKibA62IFMeUJEmSyIe8DvYFeERuOsfrRd8iano7nENqQU1dRR3tqeQOUL3eqgYgEZRT2t2iaEsib0JEw/132, createdBy=66771693911, createdName=易水河, createdTime=Wed Aug 08 16:04:24 CST 2018, time=2018-08-08, status=1, ipAttribution=)]
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    2018-08-10 太阳系小猪

    好厉害,内科学,解剖学,各种课本要改版了

    0

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    2018-08-09 xxxx1054
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    2018-08-08 易水河

    真理的唯一需要不断探索

    0