R-SPONDIN2(+) mesenchymal cells form the bud tip progenitor niche during human lung development.
R-SPONDIN2(+) mesenchymal cells form the bud tip progenitor niche during human lung development.
复制标题
R-SPONDIN2（+）间充质细胞在人肺发育过程中形成芽尖祖生态位。
DOI：
10.1016/j.devcel.2022.05.010
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发表时间：
2022-07-11
影响因子：
11.8
通讯作者：
Spence, Jason R.
中科院分区：
文献类型：
--
作者：
Hein, Renee F. C.;Wu, Joshua H.;Holloway, Emily M.;Frum, Tristan;Conchola, Ansley S.;Tsai, Yu-Hwai;Wu, Angeline;Fine, Alexis S.;Miller, Alyssa J.;Szenker-Ravi, Emmanuelle;Yan, Kelley S.;Kuo, Calvin J.;Glass, Ian;Frum, Tristan;Glass, Ian;Reversade, Bruno;Spence, Jason R.
人呼吸道上皮细胞来源于发育中的肺的远端芽中的祖细胞。这些“芽尖祖细胞”受周围间充质相互信号传导的调节;然而，间充质异质性和发育中人肺的功能知之甚少。我们询问了来自多个人肺标本的单细胞RNA测序数据，并确定了发育过程中存在的高度富集WNT激动剂RSPO 2表达的间充质细胞群，我们发现相邻的芽尖祖细胞富集RSPO 2受体LGR 5。使用类器官模型、外植体培养物和FACS分离的RSPO 2+间充质的功能实验表明，RSPO 2是一种关键的生态位线索，其增强芽尖祖细胞中的WNT信号传导以支持其维持和多能性。Hein等人提出了发育中的人类远端肺的scRNA-seq，显示了间充质的转录不同群体。空间分布显示RSPO 2+间充质细胞与LGR 5+上皮芽尖物理相邻。类器官实验表明，RSPO 2+细胞产生高WNT信号环境，支持芽尖同一性和多能性。
Human respiratory epithelium is derived from a progenitor cell in the distal buds of the developing lung. These ‘bud tip progenitors’ are regulated by reciprocal signaling with surrounding mesenchyme; however, mesenchymal heterogeneity and function in the developing human lung is poorly understood. We interrogated single-cell RNA sequencing data from multiple human lung specimens and identified a mesenchymal cell population present during development that is highly enriched for expression of the WNT agonist RSPO2, and we found that adjacent bud tip progenitors are enriched for the RSPO2 receptor LGR5. Functional experiments using organoid models, explant cultures, and FACS-isolated RSPO2+ mesenchyme show that RSPO2 is a critical niche cue that potentiates WNT signaling in bud tip progenitors to support their maintenance and multipotency. Hein et al. present scRNA-seq of the developing human distal lung, showing transcriptionally distinct populations of mesenchyme. Spatial profiling showed that RSPO2+ mesenchymal cells are physically adjacent to LGR5+ epithelial bud tips. Organoid experiments revealed that RSPO2+ cells create a high WNT signaling environment, supportng bud tip identity and multipotency.
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影响因子：
3.2
作者：
El Agha E;Bellusci S
通讯作者：
Bellusci S
影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
10.5
作者：
de Lau W;Peng WC;Gros P;Clevers H
通讯作者：
Clevers H
影响因子：
4.6
作者：
Bell, Sheila M.;Schreiner, Claire M.;Whitsett, Jeffrey A.
通讯作者：
Whitsett, Jeffrey A.
DOI：
10.1165/rcmb.2012-0030oc
发表时间：
2012-10-01
影响因子：
6.4
作者：
Chen, Leiling;Acciani, Thomas;Perl, Anne-Karina T.
通讯作者：
Perl, Anne-Karina T.