A Trisomy 21 Lung Cell Atlas.
A Trisomy 21 Lung Cell Atlas.
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21 三体肺细胞图谱。
DOI：
10.1101/2023.03.30.534839
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Danopoulos,Soula
中科院分区：
文献类型：
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作者：
Bhattacharya,Soumyaroop;Cherry,Caroline;Deutsch,Gail;BirthDefectsResearchLaboratory(BDRL);Glass,IanA;Mariani,ThomasJ;Alam,DeniseAl;Danopoulos,Soula
21三体(T21)是世界范围内最常见的染色体异常，可导致唐氏综合征(DS)。虽然肺部疾病是DS发病率和死亡率的主要原因，但肺部并发症的个体发生仍然知之甚少。我们最近证实，T21肺异常，包括呼吸道分支和血管淋巴管异常，始于宫内。在这里，我们的目标是描述产前T21肺在单细胞水平上的分子变化。我们的结果表明，在组织病理学异常开始时，细胞群体的比例和基因表达的细节变化存在差异。值得注意的是，我们发现肺泡上皮祖细胞的分布发生了变化，间充质细胞中关键的细胞外基质分子被广泛诱导，内皮细胞中干扰素信号被过度激活。这份T21肺的单细胞图谱极大地扩展了我们对肺部并发症的前驱因素的理解，并应有助于减轻DS患者的呼吸系统疾病。
Trisomy 21 (T21), resulting in Down Syndrome (DS), is the most prevalent chromosomal abnormality worldwide. While pulmonary disease is a major cause of morbidity and mortality in DS, the ontogeny of pulmonary complications remains poorly understood. We recently demonstrated that T21 lung anomalies, including airway branching and vascular lymphatic abnormalities, are initiated in utero. Here, we aimed to describe molecular changes at the single cell level in prenatal T21 lungs. Our results demonstrate differences in the proportion of cell populations and detail changes in gene expression at the time of initiation of histopathological abnormalities. Notably, we identify shifts in the distribution of alveolar epithelial progenitors, widespread induction of key extracellular matrix molecules in mesenchymal cells and hyper-activation of IFN signaling in endothelial cells. This single cell atlas of T21 lungs greatly expands our understanding of antecedents to pulmonary complications and should facilitate efforts to mitigate respiratory disease in DS.