PXD071040-1

PXD071040 is an original dataset announced via ProteomeXchange.

Title	Lamin A/C-regulated cysteine catabolic flux orchestrates cell fate through epigenome reprogramming
Description	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 pluripotent stem cells upregulates CTH and CBS enzyme expression, 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, 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.
HostingRepository	PRIDE
AnnounceDate	2025-12-04
AnnouncementXML	Submission_2025-12-04_01:12:21.300.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD071040
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Fredy Delgado Lagos
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-21 07:21:28	ID requested
⏵ 1	2025-12-04 01:12:21	announced

10.6019/PXD071040;

submitter keyword: acetylation, histones,LMNA

Prof. Dr. Sofia-Iris Bibli
contact affiliation	Vascular Dysfunction Department European Center for Angioscience Medical Faculty Mannheim Heidelberg University
contact email	iris.bibli@medma.uni-heidelberg.de
lab head
Fredy Delgado Lagos
contact affiliation	UMM/VDYS
contact email	fredy.delgado@medma.uni-heidelberg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD071040
     1. Label: PRIDE project
     2. Name: Lamin A/C-regulated cysteine catabolic flux orchestrates cell fate through epigenome reprogramming