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Series GSE102935 Query DataSets for GSE102935
Status Public on Jun 14, 2019
Title The lncRNA Hand2os1/Uph locus orchestrates heart development through regulation of precise expression HAND2
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Exploration and dissection of potential actions and effects of long noncoding RNA (lncRNA) in animals remain challenging. Here using multiple knockout mouse models and single-cell RNA sequencing, we demonstrate that the divergent lncRNA Hand2os1/Uph has a key, complex modulatory effect on the expression of its neighboring gene HAND2 and subsequently on heart development and function. Short deletion of the Hand2os1 promoter in mouse diminishes Hand2os1 transcription to 8~32%, but fails to affect HAND2 expression and yields no discernable heart phenotypes. Interestingly, full-length deletion of Hand2os1 in mouse causes moderate yet prevalent upregulation of HAND2 in hundreds of cardiac cells, leading to profound biological consequences, including dysregulated cardiac gene programs, congenital heart defects and perinatal lethality. We propose that the Hand2os1 locus dampens HAND2 expression to restrain cardiomyocyte proliferation, thereby orchestrating a balanced development of cardiac cell lineages. This study highlights the regulatory complexity of the lncRNA Hand2os1 on HAND2 expression, emphasizing the need for complementary genetic and single-cell approaches to delineate the function and primary molecular effects of an lncRNA in animals.
Overall design All RNA-seq(s) were designed to reveal the differentially expressed genes between control (heterozygous or wildtype) and homozygous Hand2as KO mice heart tissues. Allele F = full-length KO allele. Allele D = 3' Distal KO allele.
Contributor(s) Han X, Zhang J, Fan X, Luo Y, Tang F, He A, Shen X
Citation(s) 31273086
Submission date Aug 22, 2017
Last update date Sep 19, 2019
Contact name Xue Han
Organization name Tsinghua University
Department School of Medicine
Lab Shen Xiaohua Lab
Street address Zhongguancun North Street
City Beijing
ZIP/Postal code 100084
Country China
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL21273 HiSeq X Ten (Mus musculus)
Samples (27)
GSM2750799 Hand2asF/+_rep1 E11.5
GSM2750800 Hand2asF/+_rep2 E11.5
GSM2750801 Hand2asF/+_rep3 E11.5
BioProject PRJNA399498
SRA SRP115938

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Supplementary file Size Download File type/resource
GSE102935_Single-cell_mRNA_profiling_Hand2as_KO_embryonic_hearts.txt.gz 16.5 Mb (ftp)(http) TXT
GSE102935_mRNA_profiling_Hand2as_KO_heart_tissues.txt.gz 804.3 Kb (ftp)(http) TXT
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