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Myocardial Reprogramming by HMGN1 Underlies Heart Defects in Trisomy 21 [scRNA-seq]

ABSTRACT: Myocardial Reprogramming by HMGN1 Underlies Heart Defects in Trisomy 21 [scRNA-seq]

PROVIDER: PRJNA1312080 | ENA |

REPOSITORIES: ENA

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Myocardial Reprogramming by HMGN1 Underlies Heart Defects in Trisomy 21

Project description:Myocardial Reprogramming by HMGN1 Underlies Heart Defects in Trisomy 21

| PRJNA1131436 | ENA

Myocardial Reprogramming by HMGN1 Underlies Heart Defects in Trisomy 21 (CutnRun)

Project description:Myocardial Reprogramming by HMGN1 Underlies Heart Defects in Trisomy 21 (CutnRun)

| PRJNA1312066 | ENA

Myocardial Reprogramming by HMGN1 Underlies Heart Defects in Trisomy 21 (CutnRun)

Project description:Congenital heart defects (CHD) are the most common form of developmental abnormalities, occurring in ~1% of live births, and can arise due to altered dosage of genes essential for cardiogenesis. Aneuploidy accounts for nearly 15% of CHD and the most frequent form involves trisomy of chromosome 21 (Ch21), resulting in Down Syndrome (DS). Here we used single cell RNA-seq, CRISPR-activation with single cell RNA-seq, single cell ATAC-seq and Cut&Tag epigenomic profiling to define the molecular disruptions occuring with Trisomy 21 and upregulation of the Ch21 epigenetic factor HMGN1. These experiments were performed in human pluripotent stem cells (hiPSCs) or in directed differentiation to cardiomyocyte lineages at days 10 and 20.

2025-08-28 | GSE306763 | GEO

Myocardial Reprogramming by HMGN1 Underlies Heart Defects in Trisomy 21 [scRNA-seq]

2025-08-28 | GSE306773 | GEO

Trisomy of a ‘Down syndrome critical region’ globally amplifies transcription via HMGN1 overexpression [ChIP-Seq]

Project description:Down syndrome (DS, trisomy 21) is associated with developmental abnormalities and increased leukemia risk. To reconcile chromatin alterations with transcriptome changes in cells with trisomy 21, we performed paired exogenous spike-in normalized RNA and chromatin immunoprecipitation sequencing in DS models. Absolute per cell normalization unmasked global amplification of gene expression associated with trisomy 21. Overexpression of the nucleosome binding protein HMGN1 (encoded on chr21q22) recapitulated the transcriptional changes seen with triplication of a “Down syndrome critical region” on distal chromosome 21. Absolute exogenous normalized ChIP-seq (ChIP-Rx) also revealed a global increase in histone 3 lysine 27 acetylation caused by HMGN1. Genes most amplified downstream of HMGN1 were enriched for tumor- and developmental stage-specific programs of B-cell acute lymphoblastic leukemia dependent on the cellular context. These data offer a mechanistic explanation for DS transcriptional patterns, and suggest that further study of HMGN1 and RNA amplification in diverse DS phenotypes is warranted.

2018-11-13 | GSE121062 | GEO

Trisomy of a ‘Down syndrome critical region’ globally amplifies transcription via HMGN1 overexpression [SLAM-Seq]

2018-11-13 | GSE121070 | GEO

Myocardial Reprogramming by HMGN1 Underlies Heart Defects in Trisomy 21

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-08-25 | GSE271447 | GEO

Trisomy of a ‘Down syndrome critical region’ globally amplifies transcription via HMGN1 overexpression [NALM6 RNA-Seq]

2018-11-13 | GSE121065 | GEO

Trisomy of a ‘Down syndrome critical region’ globally amplifies transcription via HMGN1 overexpression [proB RNA-Seq]

2018-11-13 | GSE121066 | GEO

A CRISPR-Activation CROP-seq Screen Identifies HMGN1 as a Dosage Sensitive Regulator of Heart Defects in Down Syndrome (scATAC-Seq)

2025-08-26 | GSE271445 | GEO