Year: 2020
Type: article
Abstract: 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.
Source: Communications Biology
Authors: Amber N. Habowski, Jessica L. Flesher, Jennifer M. Bates, Chia-Feng Tsai, Kendall Martin, Rui Zhao, Anand K. Ganesan, Robert A. Edwards, Tujin Shi, H. Steven Wiley, Yongsheng Shi, Klemens J. Hertel, Marian L. Waterman
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,290
Funders: National Science Foundation, U.S. Department of Health and Human Services, Cancer Research Institute, National Institutes of Health, Directorate for Biological Sciences, University of California, Irvine, National Cancer Institute, National Institute of General Medical Sciences, National Center for Research Resources, Chao Family Comprehensive Cancer Center, Pacific Northwest National Laboratory
Awards: G1315042094, G1738746289, G1871582964, G1902661011, Reverse Sensitivity Analysis for Identifying Predictive Proteomics Signatures of Cancer, G2073767118, G2224850513, Coordinated regulation of alternative pre-mRNA processing in colon cancer, High-Throughput DNA Sequencer, G2947711961, G3786547764, G3956374251, G3968198911, Characterization of the mammalian mRNA 3'-end processing complex, G4446115863, Graduate Research Fellowship Program (GRFP), G4631142862, G5082003778, Mechanisms of Enhancer Dependent SpliceSite Activation, G5339497625, High Throughput DNA Sequencer, G5849328965, G5980120469, G6298293109, An ultrasensitive targeted mass spectrometry system for proteomics analysis of single cells, Complexity, Cooperation and Community in Cancer, G7749656634, G8094774437, PacBio RS Single Molecule, Real-Time (SMRT) DNA Sequencer, G8969961858, Identifying Therapeutic Targets for Stage III Melanoma, Mechanisms and regulation of mRNA 3' processing, Cancer Center Support Grant, A Training Program for Interdisciplinary Cancer Research
OpenAlex ID: W3076777355