Sox2 regulates globose basal cell regeneration in the olfactory epithelium.

Sox2 regulates globose basal cell regeneration in the olfactory epithelium.
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DOI:
10.1002/alr.22890
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发表时间:
2022-03
影响因子:
6.4
通讯作者:
Lane AP
Lane AP
中科院分区:
医学1区
文献类型:
--
作者:
Li Z;Wei M;Shen W;Kulaga H;Chen M;Lane AP

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在嗅觉上皮中,有丝分裂活性的球状基底细胞(GBCs)不断地补充生命中丢失的嗅觉感觉神经元。虽然转录因子Sox2在扩增嗅觉祖细胞/干细胞中的重要作用已被证实,但其在嗅觉GBCs中的确切作用仍不完全清楚。我们使用Lgr5EGFP-IRES-creERT2菌株在正常条件下和病变再生模型中表征了Sox2在嗅觉GBCs中的表达。在gbc介导的再生过程中,通过基因缺失sox2和谱系追踪实验来检测sox2在Lgr5-EGFP+ GBCs后代中的功能。在正常或再生条件下,超过95%的Lgr5-EGFP+ GBCs表达Sox2。Sox2的缺失显著减少了每个谱系追踪簇中的细胞数量。在Lgr5-EGFP+ GBCs的后代中,Sox2的缺失显著降低了OMP+嗅觉感觉神经元的比例。然而,支撑细胞的产生没有改变。我们的观察结果支持Sox2在成人嗅觉再生中的重要作用,可能作用于神经元谱系的GBCs。
In the olfactory epithelium, mitotically active globose basal cells (GBCs) continuously replenish olfactory sensory neurons lost throughout life. Although an essential role of the transcription factor Sox2 in expanding olfactory progenitors/stem cells has been shown, its precise role in olfactory GBCs remain incompletely understood. We characterized the Sox2 expression in olfactory GBCs in normal conditions and in a lesion-regeneration model using a Lgr5EGFP-IRES-creERT2 strain. During GBC-mediated regeneration, genetic deletion of sox2 and lineage tracing experiments were performed to examine the function of Sox2 in the progeny of Lgr5-EGFP+ GBCs. Over 95% of Lgr5-EGFP+ GBCs express Sox2 in normal or regeneration conditions. Loss of Sox2 dramatically reduces the cell number in each lineage traced cluster. In the progeny of Lgr5-EGFP+ GBCs, loss of Sox2 significantly decreased the portion of OMP+ olfactory sensory neurons. However, the generation of sustentacular cells was unchanged. Our observations support an essential role of Sox2 in adult olfactory regeneration, likely acting on neuronal-lineage GBCs.
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