Prenatal histological, cellular, and molecular anomalies in trisomy 21 lung.
Prenatal histological, cellular, and molecular anomalies in trisomy 21 lung.
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21三体肺的产前组织学、细胞和分子异常。
DOI：
10.1002/path.5735
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发表时间：
2021-09
期刊：
影响因子：
--
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中科院分区：
文献类型：
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唐氏综合征（DS），也称为21三体（T21），是最常见的人类染色体异常。虽然DS可以影响许多器官系统，但肺部和心脏病是死亡的主要原因。大量的现有数据表明，肺异常起源于出生后的DS。然而，一个单一的报告，分支不足的DS推断一个潜在的产前起源。由经验丰富的病理学家评估T21胎肺（n= 15）的组织学。使用免疫组织化学（IHC）检查细胞表型的空间差异。使用高通量RNA测序（RNAseq）进行产前T21肺（n= 19）和年龄匹配对照（n= 19）中的综合基因表达，并通过RT-qPCR进行验证。在分析的T21产前肺样本中，约有一半观察到组织学异常，包括末端气道/腺泡小管扩张、支气管扩张和动脉壁增厚。Ki 67的IHC显示上皮细胞和间充质细胞增殖显著减少，主要在显示病理的组织中。IHC显示，近端气道中的气道平滑肌减少且不连续，同时SOX 2减少。RNAseq在未调整时在T21肺中鉴定出118个基因显著失调（FDR < 0.05），并且在针对年龄调整时鉴定出316个基因。本体分析表明，IFN途径基因明显上调，而补体和凝血级联和细胞外基质途径基因下调。RT-qPCR证实了产前T21肺中与这些途径相关的基因的变化。我们的数据表明，特定的组织学，细胞和分子异常发生产前在不同的隔间的人T21肺，这可能是代表过早的阶段进展。
Down syndrome (DS), also known as trisomy 21 (T21), is the most common human chromosomal anomaly. Although DS can affect many organ systems, lung and heart disease are the leading causes of death. An abundance of existing data suggests that lung abnormalities originate postnatally in DS. However, a single report of branching insufficiency in DS has inferred a potential prenatal origin. The histology of T21 fetal lungs (n= 15) was assessed by an experienced pathologist. Spatial differences in cellular phenotypes were examined using immunohistochemistry (IHC). Comprehensive gene expression in prenatal T21 lungs (n= 19), and age-matched controls (n= 19), was performed using high-throughput RNA sequencing (RNAseq) and validated by RT-qPCR. Histopathological abnormalities were observed in approximately half of T21 prenatal lung samples analyzed, which included dilated terminal airways/acinar tubules, dilated lymphatics, and arterial wall thickening. IHC for Ki67 revealed significant reductions in epithelial and mesenchymal cell proliferation, predominantly in tissues displaying pathology. IHC demonstrated that airway smooth muscle was reduced and discontinuous in the proximal airway in conjunction with reduced SOX2. RNAseq identified 118 genes significantly dysregulated (FDR < 0.05) in T21 lung when unadjusted and 316 genes when adjusted for age. Ontology analysis showed that IFN pathway genes were appreciably upregulated, whereas complement and coagulation cascades and extracellular matrix pathway genes were downregulated. RT-qPCR confirmed the changes in genes associated with these pathways in prenatal T21 lungs. Our data demonstrate that specific histological, cellular, and molecular abnormalities occur prenatally in different compartments of human T21 lung, which could be representative of premature stage progression.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
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作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
14.9
作者：
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通讯作者：
Ma'ayan A
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影响因子：
5.8
作者：
Lu, Tiantian;Lin, Xiaotian;Zhang, Wei
通讯作者：
Zhang, Wei
DOI：
10.1183/16000617.0098-2016
发表时间：
2017-01
期刊：
European respiratory review : an official journal of the European Respiratory Society
影响因子：
--
作者：
通讯作者：
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影响因子：
4.4
作者：
Conti, Anna;Fabbrini, Floriana;Nitsch, Lucio
通讯作者：
Nitsch, Lucio