PXD049332

PXD049332 is an original dataset announced via ProteomeXchange.

Title	LIN28a modulates ESC differentiation by interacting with PRC2
Description	LIN28a is an RNA binding protein that was initially characterized for its role in the negative regulation of let-7 microRNA biogenesis. In the last years a new role in the regulation of mRNA translation has been highlighted. This mechanism seems to be particularly relevant in the exit of embryonic stem cells (ESCs) from the naïve state and in the first phases of differentiation process. We have demonstrated that in the first step of ESC differentiation, i.e. the establishment of epiblast-like-cells and the formation of neural precursors, LIN28a enhances the translation of de novo DNA methyltransferase Dnmt3a [1] and blocks that of the chromatin architectural factor Hmga2 [2]. How LIN28a fulfils these opposite functions in ESC differentiation is still unknown. Our preliminary results indicated that LIN28a contributes in several ways to guide ESC differentiation possibly by changing molecular partners and regulating different targets. To explore this idea, we have generated Lin28a KO ESCs using CRISPR-Cas9 technology to study how Lin28a contributes to ESC differentiation. We have found that Lin28a KO ESCs are not able to properly exit from the naïve state to undergo a differentiation program. This effect seems to be due to the impairment of different cellular processes. To better characterize this role in ESC fate we have analyzed the molecular interactions of LIN28a at different steps of ESC differentiation through proteomics approaches. Moreover, to identify the direct mRNA targets of LIN28a we are developing an iCLIP protocol suitable to analyze the binding of LIN28a to RNAs during ESC differentiation. These data coupled with the phenotypic and proteomics analysis will contribute to understand the emerging fundamental role of RNA binding proteins in differentiation and development.
HostingRepository	PRIDE
AnnounceDate	2026-05-05
AnnouncementXML	Submission_2026-05-05_13:44:26.453.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	CHIARA D'AMBROSIO
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-12 06:15:00	ID requested
⏵ 1	2026-05-05 13:44:27	announced

10.1038/S41418-026-01753-2;

submitter keyword: Lin28a, interactome, embryonic stem cells, RNA binding protein

Andrea Scaloni
contact affiliation	Istituto per il Sistema Produzione Animale in Ambiente Mediterraneo
contact email	andrea.scaloni@cnr.it
lab head
CHIARA D'AMBROSIO
contact affiliation	ISPAAM CNR
contact email	chiara.dambrosio@cnr.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD049332
     1. Label: PRIDE project
     2. Name: LIN28a modulates ESC differentiation by interacting with PRC2