Single-Cell RNA Sequencing Reveals Heterogeneity of Myf5-Derived Cells and Altered Myogenic Fate in the Absence of SRSF2.
Single-Cell RNA Sequencing Reveals Heterogeneity of Myf5-Derived Cells and Altered Myogenic Fate in the Absence of SRSF2.
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DOI：
10.1002/advs.202105775
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发表时间：
2022-06
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影响因子：
--
通讯作者：
中科院分区：
文献类型：
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剪接因子SRSF2是细胞存活的关键调节因子，然而，SRSF2是否参与成肌细胞增殖和肌肉发生尚不清楚。在这里，在成肌细胞中敲低SRSF2会导致高凋亡率和分化缺陷。结合条件敲除和谱系追踪方法表明，缺乏SRSF2的Myf5‐cre小鼠在出生时立即死亡，并表现出完全缺乏成熟肌纤维。突变的Myf5衍生细胞（tdtomato阳性细胞）随机分布在肌源区和非肌源区，表明骨骼肌分化所需的群体效应缺失。单细胞RNA测序显示，在缺乏SRSF2的情况下，myf5衍生细胞和非肌源性细胞的异质性显著增加，而骨骼肌细胞的异质性则显著增加，这反映了细胞命运的改变。研究表明，SRSF2可调节Myf5细胞进入肌生成程序，并通过防止早熟分化和凋亡来确保其存活。综上所述，SRSF2作为Myf5来源的细胞正确响应位置信号并采用其肌源性命运的重要调节因子。剪接因子SRSF2在成肌细胞增殖和分化中起关键作用。Myf5来源细胞中SRSF2的缺失会导致严重的肌原性缺陷。谱系追踪和单细胞RNA测序表明，Myf5来源的细胞具有很大的异质性。SRSF2调节Myf5细胞进入成肌程序，并通过阻止未成熟分化和凋亡来确保其存活。
Splicing factor SRSF2 acts as a critical regulator for cell survival, however, it remains unknown whether SRSF2 is involved in myoblast proliferation and myogenesis. Here, knockdown of SRSF2 in myoblasts causes high rates of apoptosis and defective differentiation. Combined conditional knockout and lineage tracing approaches show that Myf5‐cre mice lacking SRSF2 die immediately at birth and exhibit a complete absence of mature myofibers. Mutant Myf5‐derived cells (tdtomato‐positive cells) are randomly scattered in the myogenic and non‐myogenic regions, indicating loss of the community effect required for skeletal muscle differentiation. Single‐cell RNA‐sequencing reveals high heterogeneity of myf5‐derived cells and non‐myogenic cells are significantly increased at the expense of skeletal muscle cells in the absence of SRSF2, reflecting altered cell fate. SRSF2 is demonstrated to regulate the entry of Myf5 cells into the myogenic program and ensures their survival by preventing precocious differentiation and apoptosis. In summary, SRSF2 functions as an essential regulator for Myf5‐derived cells to respond correctly to positional cues and to adopt their myogenic fate. Splicing factor SRSF2 plays a key role in myoblast proliferation and differentiation. Loss of SRSF2 in Myf5‐derived cells causes severe myogenic defects. Lineage tracing and single‐cell RNA sequencing shows that Myf5‐derived cells have great heterogeneity. SRSF2 regulates Myf5 cells to enter the myogenic program and ensures their survival by preventing immature differentiation and apoptosis.
影响因子：
5.9
作者：
Iribar H;Pérez-López V;Etxaniz U;Gutiérrez-Rivera A;Izeta A
通讯作者：
Izeta A