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| Status |
Public on Jun 01, 2019 |
| Title |
E11.5 Hand1 myocardial knockout RNA-Seq |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Aims: To examine the role of the basic Helix-loop-Helix (bHLH) transcription factor HAND1 in embryonic and adult myocardium.
Methods and Results: Hand1 is expressed within the cardiomyocytes of the left ventricle (LV) and myocardial cuff between embryonic days (E) 9.5-13.5. Hand gene dosage plays an important role in ventricular morphology and the contribution of Hand1 to congenital heart defects requires further interrogation. Conditional ablation of Hand1 was carried out using either Nkx2.5 knockin Cre (Nkx2.5Cre) or a-myosin heavy chain Cre (aMhc-Cre) driver. Interrogation of transcriptome data via Ingenuity Pathway Analysis (IPA) reveals several gene regulatory pathways disrupted including translation and cardiac hypertrophy-related pathways. Embryo and adult hearts were subjected to histological, functional and molecular analyses. Myocardial deletion of Hand1 results in morphological defects that include cardiac conduction system defects, survivable interventricular septal defects (VSDs), and abnormal LV papillary muscles (PM). Resulting Hand1 conditional mutants are born at Mendelian frequencies; but the morphological alterations acquired during cardiac development result in, the mice developing diastolic heart failure.
Conclusions: Collectively, these data reveal that Hand1 contributes to the morphogenic patterning and maturation of cardiomyocytes during embryogenesis and although survivable, indicate a role for Hand1 conduction system and papillary morphogenesis.
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| Overall design |
The goal is to understand changes in gene expression in loss-of-function Hand1 hearts
RNA-seq profiling of Hand1 flox mice and Nkx2.5^Cre mice control Nkx2.5^Cre; Hand1^f/f mice ventricles.
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| |
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| Contributor(s) |
Firulli AB, Firulli BA, Gao H |
| Citation(s) |
31286141 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| P01 HL134599 |
Morphogenesis and growth of the ventricular wall in development and disease |
INDIANA UNIVERSITY |
Anthony B. Firulli |
| R01 HL145060 |
Transcriptional regulation of cardiac conduction system morphogenesis |
INDIANA UNIVERSITY |
Anthony B. Firulli |
|
| |
| Submission date |
Mar 19, 2019 |
| Last update date |
Sep 02, 2019 |
| Contact name |
Anthony Firulli |
| E-mail(s) |
tfirulli@iu.edu
|
| Phone |
317-278-5814
|
| Organization name |
Indiana University School of Medicine
|
| Department |
Pediatrics - Wells Center
|
| Lab |
Firulli lab
|
| Street address |
1044 W Walnut R4 351
|
| City |
Indianapolis |
| State/province |
IN |
| ZIP/Postal code |
46256 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (7)
|
| GSM3680390 |
E11.5 ventricle _Nkx Cre +/-; H1flox/flox (NT-1) |
| GSM3680391 |
E11.5 ventricle _Nkx Cre +/-; H1flox/flox (NT-6 ) |
| GSM3680392 |
E11.5 ventricle _Nkx Cre wt; H1flox/flox (310-4) |
| GSM3680393 |
E11.5 ventricle _Nkx Cre wt; H1flox/flox (NT-7) |
| GSM3680394 |
E11.5 ventricle _Nkx Cre +/-; wt (10R-2) |
| GSM3680395 |
E11.5 ventricle _Nkx Cre +/-; wt (83-1) |
| GSM3680396 |
E11.5 ventricle _Nkx Cre +/-; wt (10R-6) |
|
| Relations |
| BioProject |
PRJNA528178 |
| SRA |
SRP188922 |
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