Myoepithelial Cells of Submucosal Glands Can Function as Reserve Stem Cells to Regenerate Airways after Injury.
Myoepithelial Cells of Submucosal Glands Can Function as Reserve Stem Cells to Regenerate Airways after Injury.
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DOI：
10.1016/j.stem.2018.03.018
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发表时间：
2018-05-03
期刊：
影响因子：
23.9
通讯作者：
Tata PR
中科院分区：
文献类型：
--
作者：
Tata A;Kobayashi Y;Chow RD;Tran J;Desai A;Massri AJ;McCord TJ;Gunn MD;Tata PR
细胞在损伤后表现出可塑性，但这种现象的程度和所涉及的细胞机制仍未得到充分探讨。通过单细胞RNA测序（scRNA-seq）和谱系追踪，我们发现在多种损伤模型中，粘膜下腺（SMGs）的肌上皮细胞（mec）增殖和迁移以重新填充气道表面上皮（SE）。具体来说，smg来源的细胞表现出多能性，并有助于smg和SE的基底和腔细胞类型。体外扩增的mec有可能在移植到剥离的气道支架上时重新填充并分化为SE细胞。值得注意的是，我们发现在严重损伤的大动物肺小叶外和小叶内气道的SE上都出现了smg样细胞。我们发现转录因子SOX9是气道再生中MEC可塑性所必需的。由于smg丰富且存在于气道深处，它们可能作为促进人体气道再生的储备细胞来源。气道粘膜下腺是粘膜和抗微生物产物的储存库，提供对微生物的防御。在这里，Tata和他的同事们发现了smg中一个隐藏的储备多能干细胞群，它们可以通过SOX9依赖的转录程序增殖、迁移和转分化来修复损伤后的表面上皮。
Cells demonstrate plasticity following injury, but the extent of this phenomenon and the cellular mechanisms involved remain underexplored. Using single cell RNA sequencing (scRNA-seq) and lineage tracing, we uncover that myoepithelial cells (MECs) of the submucosal glands (SMGs) proliferate and migrate to repopulate the airway surface epithelium (SE) in multiple injury models. Specifically, SMG-derived cells display multipotency and contribute to basal and luminal cell types of the SMGs and SE. Ex vivo expanded MECs have the potential to repopulate and differentiate into SE cells when grafted onto denuded airway scaffolds. Significantly, we find that SMG-like cells appear on the SE of both extra- and intra-lobular airways of large animal lungs following severe injury. We find that the transcription factor SOX9 is necessary for MEC plasticity in airway regeneration. Since SMGs are abundant and present deep within airways, they may serve as a reserve cell source for enhancing human airway regeneration. Airway submucosal glands are reservoirs of mucous and anti-microbial products that provide defense against microbes. Here, Tata and colleagues uncover a hidden reserve multipotent stem cell population in SMGs that can proliferate, migrate, and transdifferentiate to repair surface epithelium following injury through a SOX9 dependent transcriptional program.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
4
作者：
Hegab, Ahmed E.;Kubo, Hiroshi;Yamaya, Mutsuo
通讯作者：
Yamaya, Mutsuo
DOI：
10.1513/pats.200803-025hr
发表时间：
2008-09-15
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Franks, Teri J;Colby, Thomas V;Williams, Mary C
通讯作者：
Williams, Mary C
DOI：
10.1126/science.1242281
发表时间：
2014-06-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Blanpain C;Fuchs E
通讯作者：
Fuchs E
影响因子：
64.5
作者：
Hsu YC;Pasolli HA;Fuchs E
通讯作者：
Fuchs E