A Hierarchy of Proliferative and Migratory Keratinocytes Maintains the Tympanic Membrane.
A Hierarchy of Proliferative and Migratory Keratinocytes Maintains the Tympanic Membrane.
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增殖和迁移的角质形成细胞维持鼓膜。
DOI：
10.1016/j.stem.2020.10.006
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发表时间：
2021-02-04
期刊：
影响因子：
23.9
通讯作者：
Tward AD
中科院分区：
文献类型：
--
作者：
Frumm SM;Yu SK;Chang J;Artichoker JA;Scaria SM;Lee KP;Byrnes LE;Sneddon JB;Tward AD
鼓膜（TM）对听力至关重要，需要持续清除细胞碎片，但对TM表皮的稳态机制知之甚少。使用单细胞RNA测序，谱系追踪，全器官外植体，和活细胞成像，我们表明，稳态TM表皮是不同于其他表皮网站，并具有离散的增殖区与三维层次的多个角质形成细胞群体。TM干细胞位于上级TM的离散位置，并产生长寿克隆和定向祖细胞（CP）。CP克隆表现出侧向迁移，并且它们的增殖能力得到Pdgfra+成纤维细胞的支持，产生迁移但非增殖的后代。人TM的单细胞测序揭示了相似的细胞类型和转录编程。因此，在体内平衡期间，TM角质形成细胞通过增殖CP状态过渡并表现出定向侧向迁移。这项工作为理解TM疾病和角质形成细胞生物学建模奠定了基础。Tward及其同事发现，鼓膜（TM）表皮具有不同的干细胞和定向祖细胞区域。在稳态中，角质形成细胞迁移穿过TM以维持薄的振动表面，并且它们仅在接近支持间充质时增殖。
The tympanic membrane (TM) is critical for hearing and requires continuous clearing of cellular debris, but little is known about homeostatic mechanisms in TM epidermis. Using single-cell RNA sequencing, lineage tracing, whole-organ explant, and live-cell imaging, we show that homeostatic TM epidermis is distinct from other epidermal sites and has discrete proliferative zones with a three-dimensional hierarchy of multiple keratinocyte populations. TM stem cells reside in a discrete location of the superior TM and generate long-lived clones and committed progenitors (CPs). CP clones exhibit lateral migration and their proliferative capacity is supported by Pdgfra+ fibroblasts, generating migratory but non-proliferative progeny. Single-cell sequencing of human TM revealed similar cell types and transcriptional programming. Thus, during homeostasis, TM keratinocytes transit through a proliferative CP state and exhibit directional lateral migration. This work forms a foundation for understanding TM disorders and modeling keratinocyte biology. Tward and colleagues show that the tympanic membrane (TM) epidermis has distinct stem cell and committed progenitor regions. In homeostasis, keratinocytes migrate across the TM to maintain a thin vibratory surface, and they proliferate only when in proximity to supporting mesenchyme.
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DOI：
10.1073/pnas.1715911114
发表时间：
2018-01-23
影响因子：
11.1
作者：
Basak, Onur;Krieger, Teresa G.;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
3.4
作者：
Kato, M;Jackler, RK
通讯作者：
Jackler, RK
影响因子：
1.4
作者：
Kakoi, H;Anniko, M
通讯作者：
Anniko, M
影响因子：
2.7
作者：
Feitosa, Natalia Martins;Zhang, Jinli;Carney, Thomas J.;Metzger, Manuel;Korzh, Vladimir;Bloch, Wilhelm;Hammerschmidt, Matthias
通讯作者：
Hammerschmidt, Matthias
影响因子：
5.3
作者：
Hamilton, TG;Klinghoffer, RA;Soriano, P
通讯作者：
Soriano, P