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| Status |
Public on Feb 28, 2020 |
| Title |
Lamin B2 controls nuclear envelope permeability and regulates cardiomyocyte regeneration |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Heart muscle cells, cardiomyocytes, are highly differentiated cells that usually do not proliferate . During the non-proliferative state, extracellular signals control cardiomyocyte contractile function. However, during development and regeneration, cardiomyocytes enter the cell cycle and divide. It is unknown how cardiomyocytes modify their intracellular signaling to direct the cell cycle program. Here, we show that the nuclear lamina protein Lamin B2 (Lmnb2) regulates cardiomyocyte cell cycle activity using a gatekeeper mechanism. We identified Lmnb2 as a candidate for regulating intracellular signaling with deep transcriptional profiling of single cardiomyocytes. Lmnb2 was sufficient and necessary for cardiomyocyte cycling in the presence of serum. Lmnb2 increased the nucleoporin NUP98 and permeability of the nuclear membrane for phosphorylated ERK1/2. In vivo, the Lmnb2 gene was required for cardiomyocyte cell cycle activity during development. Increasing the expression of Lmnb2 in neonatal mice promoted cardiomyocyte M-phase and cytokinesis. LmnB2 gene transfer in neonatal mice that received a myocardial injury increased cardiomyocyte division and myocardial function in the injury border zone, indicating that the regenerated cardiomyocytes were functionally integrated. We propose a gatekeeper function of Lmnb2 that can be targeted to increase cardiomyocyte regeneration without the administration of exogenous growth factors.
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| Overall design |
The cardiomyocytes were isolated from embryonic (E14.5) and postnatal (P19) mouse (FUCCI) hearts, then the single cardiomyocytes were collected through FACS. The cycling cardiomyocytes were identified through Azami Green-Geminin (mAG-hGem) signal. The mRNA was amplified using the antisense RNA (aRNA) amplification method.
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| Contributor(s) |
Choudhury S, Ganapathy B, Ammanamanchi N, Suresh S, Polizzotti BD, Khaladkar M, Singh J, Maehr R, Kim J, Eberwine JH, Wu Y, Kühn B |
| Citation(s) |
32109383 |
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| Submission date |
Dec 20, 2017 |
| Last update date |
Mar 02, 2020 |
| Contact name |
Junhyong Kim |
| Organization name |
University of Pennsylvania
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| Department |
Biology
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| Lab |
Junhyong Kim
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| Street address |
433 S University Avenue
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (33)
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| Relations |
| BioProject |
PRJNA423262 |
| SRA |
SRP127261 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE108360_Lmnb2_cnts.csv.gz |
650.0 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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