ArticlePloS one2015
A systems biology approach identifies a regulatory network in parotid acinar cell terminal differentiation.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Article
- RNA-sequencing data-driven dissection of human plasma cell differentiation reveals new potential transcription regulators.Leukemia · 2021Article
- Early Emergence of Adaptive Mechanisms Sustaining Ig Production: Application to Antibody Therapy.Frontiers in immunology · 2021Review
- Article
- A single transcription factor is sufficient to induce and maintain secretory cell architecture.Genes & development · 2017Article
- Uncovering stem cell differentiation factors for salivary gland regeneration by quantitative analysis of differential proteomes.PloS one · 2017Article
- Hepatocyte nuclear factor 4α is required for cell differentiation and homeostasis in the adult mouse gastric epithelium.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Use of multiple time points to model parotid differentiation.Genomics data · 2015Article
- Correction: a systems biology approach identifies a regulatory network in parotid acinar cell terminal differentiation.PloS one · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
objectiveThe transcription factor networks that drive parotid salivary gland progenitor cells to terminally differentiate, remain largely unknown and are vital to understanding the regeneration process. METHODOLOGY: A systems biology approach was taken to measure mRNA and microRNA expression in vivo across acinar cell terminal differentiation in the rat parotid salivary gland. Laser capture microdissection (LCM) was used to specifically isolate acinar cell RNA at times spanning the month-long period of parotid differentiation.
resultsClustering of microarray measurements suggests that expression occurs in four stages. mRNA expression patterns suggest a novel role for Pparg which is transiently increased during mid postnatal differentiation in concert with several target gene mRNAs. 79 microRNAs are significantly differentially expressed across time. Profiles of statistically significant changes of mRNA expression, combined with reciprocal correlations of microRNAs and their target mRNAs, suggest a putative network involving Klf4, a differentiation inhibiting transcription factor, which decreases as several targeting microRNAs increase late in differentiation. The network suggests a molecular switch (involving Prdm1, Sox11, Pax5, miR-200a, and miR-30a) progressively decreases repression of Xbp1 gene transcription, in concert with decreased translational repression by miR-214. The transcription factor Xbp1 mRNA is initially low, increases progressively, and may be maintained by a positive feedback loop with Atf6. Transfection studies show that Xbp1 activates the Mist1 promoter [corrected]. In addition, Xbp1 and Mist1 each activate the parotid secretory protein (Psp) gene, which encodes an abundant salivary protein, and is a marker of terminal differentiation.
conclusionThis study identifies novel expression patterns of Pparg, Klf4, and Sox11 during parotid acinar cell differentiation, as well as numerous differentially expressed microRNAs. Network analysis identifies a novel stemness arm, a genetic switch involving transcription factors and microRNAs, and transition to an Xbp1 driven differentiation network. This proposed network suggests key regulatory interactions in parotid gland terminal differentiation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.