Ascl3 transcription factor marks a distinct progenitor lineage for non-neuronal support cells in the olfactory epithelium.

Ascl3 transcription factor marks a distinct progenitor lineage for non-neuronal support cells in the olfactory epithelium.
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DOI:
10.1038/srep38199
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发表时间:
2016-12-02
期刊:
影响因子:
4.6
通讯作者:
Ovitt CE
Ovitt CE
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Weng PL;Vinjamuri M;Ovitt CE

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嗅觉上皮(OE)由嗅觉感觉神经元(OSNs)、支持细胞和多种非神经细胞组成。干细胞和祖细胞位于基底部,是维持OE内环境稳定所需的所有细胞类型的来源。在这里,我们报道了一种基本的螺旋-环-螺旋转录因子Ascl3在发育中的OE中表达。谱系追踪实验表明,非神经元微绒毛细胞和鲍曼腺在发育过程中仅来源于OE中的AsCl3+祖细胞。在化学损伤后,Ascl3在水平基底细胞(HbCs)中的表达被激活,在OE再生过程中,HbCs重新填充所有的微绒毛细胞和Bowman腺体。去掉表达Ascl3的细胞后,OE可以再生,但缺乏非神经元微绒毛和Bowman腺支持细胞。这些结果表明,Ascl3标记了严格依系于微绒毛细胞和鲍曼腺的祖细胞,并强调了这些细胞类型支持OE动态平衡的要求。
The olfactory epithelium (OE) is composed of olfactory sensory neurons (OSNs), sustentacular supporting cells, and several types of non-neuronal cells. Stem and progenitor cells are located basally, and are the source of all cell types needed to maintain OE homeostasis. Here, we report that Ascl3, a basic helix-loop-helix transcription factor, is expressed in the developing OE. Lineage tracing experiments demonstrate that the non-neuronal microvillar cells and Bowman’s glands are exclusively derived from Ascl3+ progenitor cells in the OE during development. Following chemically-induced injury, Ascl3 expression is activated in a subset of horizontal basal cells (HBCs), which repopulate all microvillar cells and Bowman’s glands during OE regeneration. After ablation of Ascl3-expressing cells, the OE can regenerate, but lacks the non-neuronal microvillar and Bowman’s gland support cells. These results demonstrate that Ascl3 marks progenitors that are lineage-committed strictly to microvillar cells and Bowman’s glands, and highlight the requirement for these cell types to support OE homeostasis.
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