FOS licenses early events in stem cell activation driving skeletal muscle regeneration.
FOS licenses early events in stem cell activation driving skeletal muscle regeneration.
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DOI：
10.1016/j.celrep.2020.108656
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发表时间：
2021-01-26
期刊：
影响因子：
8.8
通讯作者：
Wagers, Amy J.
中科院分区：
文献类型：
--
作者：
Almada, Albert E.;Horwitz, Naftali;Price, Feodor D.;Gonzalez, Alfredo E.;Ko, Michelle;Bolukbasi, Ozge Vargel;Messemer, Kathleen A.;Chen, Sonia;Sinha, Manisha;Rubin, Lee L.;Wagers, Amy J.
肌卫星细胞（Muscle satellite cells，SC）是未损伤骨骼肌中的一种静止（非增殖）干细胞群。尽管对SC的研究已经有近60年的历史，但将静止的SC转化为快速分裂（活化）的干细胞/祖细胞的分子驱动因素在很大程度上仍然未知，这些干细胞/祖细胞介导损伤后的肌肉修复。在这里，我们确定了一个突出的FBJ骨肉瘤癌基因（Fos）的mRNA和蛋白质的签名在最近激活的SC是快速，异质性，瞬时诱导肌肉损伤。我们进一步揭示了FOS通过诱导刺激细胞迁移、分裂和分化的“促再生”靶基因来有效启动关键干细胞功能的需要，包括细胞周期进入、增殖扩增和肌肉再生。这些Fos/AP-1靶点之一，NAD（+）-消耗单ADP-核糖基转移酶1（Art 1）在SC中的破坏延迟了细胞周期的进入，并阻碍了祖细胞的扩增和肌肉再生。这项工作揭示了一个早期激活的FOS/ART 1/单ADP核糖基化（MARylation）途径，这是干细胞再生反应所必需的。成体干细胞如何被激活以修复损伤后的组织和器官仍然是再生生物学中最大的谜团之一。Almada等人揭示了一个由FOS驱动的“促再生”转录基因网络，包括NAD（+）依赖性单ADP核糖基化（MARylating）酶Art 1，它驱动有效的肌肉干细胞活化和肌肉修复。
Muscle satellite cells (SCs) are a quiescent (non-proliferative) stem cell population in uninjured skeletal muscle. Although SCs have been investigated for nearly 60 years, the molecular drivers that transform quiescent SCs into the rapidly dividing (activated) stem/progenitor cells that mediate muscle repair after injury remain largely unknown. Here we identify a prominent FBJ osteosarcoma oncogene (Fos) mRNA and protein signature in recently activated SCs that is rapidly, heterogeneously, and transiently induced by muscle damage. We further reveal a requirement for FOS to efficiently initiate key stem cell functions, including cell cycle entry, proliferative expansion, and muscle regeneration, via induction of “pro-regenerative” target genes that stimulate cell migration, division, and differentiation. Disruption of one of these Fos/AP-1 targets, NAD(+)-consuming mono-ADP-ribosyl-transferase 1 (Art1), in SCs delays cell cycle entry and impedes progenitor cell expansion and muscle regeneration. This work uncovers an early-activated FOS/ART1/mono-ADP-ribosylation (MARylation) pathway that is essential for stem cell-regenerative responses. How adult stem cells are activated to repair tissues and organs after injury remains one of the greatest mysteries in regenerative biology. Almada et al. reveal a FOS-driven “pro-regenerative” transcriptional gene network, including the NAD(+)-dependent mono-ADP-ribosylating (MARylating) enzyme Art1, that drives effective muscle stem cell activation and muscle repair.
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DOI：
10.1242/dev.100842
发表时间：
2014-04
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Chakkalakal JV;Christensen J;Xiang W;Tierney MT;Boscolo FS;Sacco A;Brack AS
通讯作者：
Brack AS
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
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：
4.6
作者：
Lepper, Christoph;Partridge, Terence A.;Fan, Chen-Ming
通讯作者：
Fan, Chen-Ming
影响因子：
--
作者：
Friedrich, Maik;Boehlig, Levin;Hauschildt, Sunna
通讯作者：
Hauschildt, Sunna