Transcriptomic and proteomic signatures of stemness and differentiation in the colon crypt.
Amber N HabowskiJessica L FlesherJennifer M BatesChia-Feng TsaiKendall MartinRui ZhaoAnand K GanesanRobert A EdwardsTujin ShiH Steven WileyYongsheng ShiKlemens J HertelMarian L WatermanPublished in: Communications biology (2020)
Intestinal stem cells are non-quiescent, dividing epithelial cells that rapidly differentiate into progenitor cells of the absorptive and secretory cell lineages. The kinetics of this process is rapid such that the epithelium is replaced weekly. To determine how the transcriptome and proteome keep pace with rapid differentiation, we developed a new cell sorting method to purify mouse colon epithelial cells. Here we show that alternative mRNA splicing and polyadenylation dominate changes in the transcriptome as stem cells differentiate into progenitors. In contrast, as progenitors differentiate into mature cell types, changes in mRNA levels dominate the transcriptome. RNA processing targets regulators of cell cycle, RNA, cell adhesion, SUMOylation, and Wnt and Notch signaling. Additionally, global proteome profiling detected >2,800 proteins and revealed RNA:protein patterns of abundance and correlation. Paired together, these data highlight new potentials for autocrine and feedback regulation and provide new insights into cell state transitions in the crypt.
Keyphrases
- single cell
- stem cells
- rna seq
- cell therapy
- cell cycle
- cell proliferation
- genome wide
- gene expression
- magnetic resonance
- magnetic resonance imaging
- machine learning
- binding protein
- electronic health record
- small molecule
- epithelial mesenchymal transition
- artificial intelligence
- signaling pathway
- sensitive detection
- protein protein
- transcription factor
- big data
- deep learning
- antibiotic resistance genes
- data analysis