Proteomics

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Quantitative Analysis of Differential Proteomes in Mouse Mesenchymal Stem Cells Converted to Salivary Epithelial Precursors


ABSTRACT: Severe hyposalivation often results from Sjögren’s syndrome or radiation therapy for head and neck cancer. Devastating consequences of hyposalivation, such as rampant dental caries and persistent oral candidiasis, compromise the quality of life in those patients. Clinical management for dry mouth typically involves simple palliative methods or secretagogues, which are designed to stimulate saliva secretion from residual salivary acinar cells present in the glands. However, direct interventions in chronic dryness have yet to be employed in the clinical setting. Despite numerous studies on salivary gland regeneration, the molecular basis governing stem cell transdifferentiation into salivary epithelial precursors (SEP) is largely unknown. Our previously published study clearly indicated mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) can be differentiated into SEP in vitro when co-cultured with isolated primary salivary gland cells without cell-to-cell contact. Our current study utilized iTRAQ-LS-MS/MS-based quantitative proteomics to profile key regulatory factors involved in mouse MSC-to-SEP conversion. We identified 280 differentially expressed proteins in BM-MSCs over the course of 7 days of co-culture. Interestingly, protein expression of salivary transcription factors (STFs), such as transcription factor E2a (TCF3), high mobility group protein 20B (HMG20b), and ankyrin repeat domain-containing protein 56 (ANKRD56) were increased in a time-dependent manner. Notably, pancreas specific transcription factor 1a (PTF1α), muscle, intestine and stomach expression-1 (MIST-1) and achaete-scute complex homolog 3(ASCL3) were newly induced over time in differentiated MSCs. We also identified the expression of Ptf1α in the mouse salivary glands for the first time and verified its expression in independent batches of co-cultured MSCs by western blotting. Furthermore, simulation of the molecular network involving the identified STFs has demonstrated evidence for their perspective roles in salivary gland development during glandular maturation. Thus, our study provides the first extensive proteomic profile of MSC-to-SEP transdifferentiation and identifies novel STFs that may be critical for this process.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Embryonic Stem Cell

DISEASE(S): Sjogren's Syndrome

SUBMITTER: Jin Koh  

LAB HEAD: Seunghee Cha

PROVIDER: PXD002796 | Pride | 2017-02-14

REPOSITORIES: pride

Dataset's files

Source:
Action DRS
Cha1-1.dat Other
Cha1-1.mzid.gz Mzid
Cha1-1.pride.mztab.gz Mztab
Cha1-10.dat Other
Cha1-10.mzid.gz Mzid
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Publications

Uncovering stem cell differentiation factors for salivary gland regeneration by quantitative analysis of differential proteomes.

Park Yun-Jong YJ   Koh Jin J   Kwon Jin Teak JT   Park Yong-Seok YS   Yang Lijun L   Cha Seunghee S  

PloS one 20170203 2


Severe xerostomia (dry mouth) compromises the quality of life in patients with Sjögren's syndrome or radiation therapy for head and neck cancer. A clinical management of xerostomia is often unsatisfactory as most interventions are palliative with limited efficacy. Following up our previous study demonstrating that mouse BM-MSCs are capable of differentiating into salivary epithelial cells in a co-culture system, we further explored the molecular basis that governs the MSC reprogramming by utiliz  ...[more]

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