Alveolar cell fate selection and lifelong maintenance of AT2 cells by FGF signaling.
Alveolar cell fate selection and lifelong maintenance of AT2 cells by FGF signaling.
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DOI：
10.1038/s41467-022-34059-1
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发表时间：
2022-11-21
影响因子：
16.6
通讯作者：
Krasnow, Mark A.
中科院分区：
文献类型：
--
作者：
Brownfield, Douglas G.;de Arce, Alex Diaz;Ghelfi, Elisa;Gillich, Astrid;Desai, Tushar J.;Krasnow, Mark A.
肺部的气体交换表面由肺泡 AT1 和 AT2 细胞组成，这些细胞在几种常见且致命的疾病中遭到破坏。它们起源于双能祖细胞，其分化被认为是由不同的机械力决定的。在这里，我们展示了关键的决定因素是 FGF 信号传导。 Fgfr2 在小鼠发育中的祖细胞中表达，然后限制在新生的 AT2 细胞中，并在整个生命过程中持续存在。其配体在周围的间质中表达，在没有外源机械信号的情况下，可以诱导祖细胞与混合的 AT2 和 AT1 细胞形成肺泡球。 FGF 信号直接传导，细胞自主指定 AT2 命运；体外和体内缺乏 Fgfr2 的祖细胞仅获得 AT1 命运。 AT2 细胞围产期 Fgfr2 缺失会导致重编程为 AT1 身份，而生命后期的缺失或抑制会触发 AT2 细胞凋亡和代偿性再生。我们认为，Fgfr2 信号在发育过程中选择 AT2 的命运，诱导细胞非自主 AT1 分化信号，然后在整个生命过程中持续维持 AT2 身份和存活。作者在此表明，FGF 信号通过诱导 AT2 命运和 AT1 命运的次级信号来启动小鼠肺中的肺泡发育，并在整个生命过程中持续维持 AT2 细胞。 FGF 抑制立即触发 AT2 凋亡和代偿性再生。
The lung’s gas exchange surface is comprised of alveolar AT1 and AT2 cells that are corrupted in several common and deadly diseases. They arise from a bipotent progenitor whose differentiation is thought to be dictated by differential mechanical forces. Here we show the critical determinant is FGF signaling. Fgfr2 is expressed in the developing progenitors in mouse then restricts to nascent AT2 cells and remains on throughout life. Its ligands are expressed in surrounding mesenchyme and can, in the absence of exogenous mechanical cues, induce progenitors to form alveolospheres with intermingled AT2 and AT1 cells. FGF signaling directly and cell autonomously specifies AT2 fate; progenitors lacking Fgfr2 in vitro and in vivo exclusively acquire AT1 fate. Fgfr2 loss in AT2 cells perinatally results in reprogramming to AT1 identity, whereas loss or inhibition later in life triggers AT2 apoptosis and compensatory regeneration. We propose that Fgfr2 signaling selects AT2 fate during development, induces a cell non-autonomous AT1 differentiation signal, then continuously maintains AT2 identity and survival throughout life. Here the authors show that FGF signaling initiates alveolus development in mouse lung by inducing AT2 fate and a secondary signal for AT1 fate, and continuously maintains AT2 cells throughout life. FGF inhibition triggers immediate AT2 apoptosis and compensatory regeneration.
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影响因子：
16.6
作者：
Alanis, Denise Martinez;Chang, Daniel R.;Akiyama, Haruhiko;Krasnow, Mark A.;Chen, Jichao
通讯作者：
Chen, Jichao
影响因子：
3.6
作者：
Foster, Cherie D.;Varghese, Linda S.;Guttentag, Susan H.
通讯作者：
Guttentag, Susan H.
影响因子：
10
作者：
Brehm JM;Hagiwara K;Tesfaigzi Y;Bruse S;Mariani TJ;Bhattacharya S;Boutaoui N;Ziniti JP;Soto-Quiros ME;Avila L;Cho MH;Himes B;Litonjua AA;Jacobson F;Bakke P;Gulsvik A;Anderson WH;Lomas DA;Forno E;Datta S;Silverman EK;Celedón JC
通讯作者：
Celedón JC
影响因子：
3.3
作者：
Franks TJ;Chong PY;Chui P;Galvin JR;Lourens RM;Reid AH;Selbs E;McEvoy CP;Hayden CD;Fukuoka J;Taubenberger JK;Travis WD
通讯作者：
Travis WD
DOI：
10.1073/pnas.1813952116
发表时间：
2019-03-05
影响因子：
11.1
作者：
Frank, David B.;Penkala, Ian J.;Morrisey, Edward E.
通讯作者：
Morrisey, Edward E.