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| Status |
Public on Nov 20, 2025 |
| Title |
Lamin A/C-regulated cysteine catabolic flux modulates stem cell fate through epigenome reprogramming [ES_ChIP_seq_H3K9me3_LA] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Spatiotemporal changes in the nuclear lamina and cell metabolism shape cell fate, yet their interplay is poorly understood. Here, we identify lamin A/C as a key regulator of cysteine catabolic flux essential for proper cell fate and longevity. Its loss in naïve mouse pluripotent stem cells leads to upregulation of the cysteine generating and catabolizing enzymes, cystathionine γ-lyase (CTH) and cystathionine β-synthase (CBS), thereby promoting de novo cysteine synthesis. Increased cysteine flux into acetyl-CoA fosters histone H3K9 and H3K27 acetylation, triggering a transition from naïve to primed pluripotency and abnormal cell fate and function. Conversely, the toxic gain-of-function mutation of Lmna, encoding lamin A/C and associated with premature aging, reduces CTH and CBS levels. This reroutes cysteine catabolic flux and alters the balance between H3K9 acetylation and methylation, crucially impacting germ layer formation and genome stability. Importantly, modulation of Cth and Cbs rescues the abnormal cell fate and function, restores the DNA damage repair capacity, and alleviates the senescent phenotype caused by lamin A/C mutations, highlighting the potential of modulating cell metabolism to mitigate epigenetic diseases.
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| Overall design |
Control, Lmna KO and Lmna G609G/G609G Nkx2-5-GFP mES cell lines were cultured on feeder condition in DMEM high glucose supplemented with 15% FCS and 1000 U/ml LIF. ESCs were harvested to perform for H3K9me3 ChIP-seq.
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| Contributor(s) |
Cordero J, Wang Y, Dobreva G |
| Citation(s) |
41606307 |
| |
| Submission date |
Oct 07, 2024 |
| Last update date |
Feb 20, 2026 |
| Contact name |
Gergana Dobreva |
| E-mail(s) |
Gergana.Dobreva@medma.uni-heidelberg.de
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| Organization name |
Medical Faculty Mannheim/University of Heidelberg
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| Department |
Cardiovascular Genomics and Epigenomics
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| Lab |
AG Dobreva
|
| Street address |
Ludolf-Krehl-Str. 7-11
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| City |
Mannheim |
| State/province |
Baden Württemberg |
| ZIP/Postal code |
68167 |
| Country |
Germany |
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| Platforms (1) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE248534 |
Lamin A/C-regulated cysteine catabolic flux modulates stem cell fate through epigenome reprogramming |
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| Relations |
| BioProject |
PRJNA1169892 |
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