Abstract
The mammalian stomach is structurally highly diverse and its organ functionality critically depends on a normal embryonic development. Although there have been several studies on the morphological changes during stomach development, a system-wide analysis of the underlying molecular changes is lacking. Here, we present a comprehensive, temporal proteome and transcriptome atlas of the mouse stomach at multiple developmental stages. Quantitative analysis of 12,108 gene products allows identifying three distinct phases based on changes in proteins and RNAs and the gain of stomach functions on a longitudinal time scale. The transcriptome indicates functionally important isoforms relevant to development and identifies several functionally unannotated novel splicing junction transcripts that we validate at the peptide level. Importantly, many proteins differentially expressed in stomach development are also significantly overexpressed in diffuse-type gastric cancer. Overall, our study provides a resource to understand stomach development and its connection to gastric cancer tumorigenesis.
Highlights
The mammalian stomach is structurally highly diverse and its organ functionality critically depends on a normal embryonic development
A total of 8,865 gene products (GPs) were identified as high-quality IDs by selecting those that have been measured with at least one unique peptide (GPs-specific sequence) and two strict peptides (Dataset[2] in Supplementary Data 1)
Housekeeping proteins (e.g., TUBB4B and HSP90B1) show stable expression across the whole developing stages, whereas proteins related to liver development (e.g., AFP and ALB) are highly dynamic and time-dependent, which suggests their widespread roles in organ development[34] (Fig. 1f)
Summary
The mammalian stomach is structurally highly diverse and its organ functionality critically depends on a normal embryonic development. Quantitative analysis of 12,108 gene products allows identifying three distinct phases based on changes in proteins and RNAs and the gain of stomach functions on a longitudinal time scale. Many proteins differentially expressed in stomach development are significantly overexpressed in diffuse-type gastric cancer. Most studies of stomach development have focused on a single or a small set of proteins or on a specific pathway. Based on these efforts, the key roles of several transcriptional regulators (e.g., BARX10, HOXA511, SOX21, CDX212, HNF1β13, PDX14, and GATA415) and signaling pathways (Wnt[16,17], retinoic acid[18], Notch[19], FGF1,3,4, BMP20, SHH15, Hippo[21], and TGF-β22) in controlling organ development have been defined. Studies have confirmed that tumorigenesis shares many similar features with deregulated embryonic development[30,31]
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