Transcriptomic and proteomic signatures of stemness and differentiation in the colon crypt

Autor: Kendall Martin, Jessica L. Flesher, Rui Zhao, Klemens J. Hertel, Chia-Feng Tsai, Amber N Habowski, Yongsheng Shi, Anand K. Ganesan, Marian L. Waterman, Tujin Shi, Robert Edwards, H. Steven Wiley, Jennifer M. Bates
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Proteomics
Proteome
Medicine (miscellaneous)
Post-Transcriptional
Regenerative Medicine
Transcriptome
Mice
0302 clinical medicine
Stem Cell Research - Nonembryonic - Human
Developmental
Flow cytometry
Intestinal Mucosa
Cell Self Renewal
lcsh:QH301-705.5
Cancer
0303 health sciences
Stem Cells
Intestinal stem cells
Wnt signaling pathway
Cell Differentiation
Cell cycle
Cell sorting
Cell biology
Colo-Rectal Cancer
Stem Cell Research - Nonembryonic - Non-Human
Stem cell
General Agricultural and Biological Sciences
RNA Processing
Colon
1.1 Normal biological development and functioning
Notch signaling pathway
Biology
General Biochemistry
Genetics and Molecular Biology
Article
Immunophenotyping
03 medical and health sciences
Underpinning research
Genetics
Animals
Progenitor cell
Transcriptomics
030304 developmental biology
Gene Expression Profiling
Human Genome
Computational Biology
Stem Cell Research
Enterocytes
Gene Expression Regulation
lcsh:Biology (General)
Generic health relevance
Digestive Diseases
030217 neurology & neurosurgery
Biomarkers
Zdroj: Communications Biology, Vol 3, Iss 1, Pp 1-17 (2020)
Communications biology, vol 3, iss 1
Communications Biology
ISSN: 2399-3642
Popis: 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.
Habowski et al. develop a sorting protocol for purification and comparative analysis of mouse colon stem cells and their progeny. By proteomic and transcriptomic analysis, they determine that lineage commitment is accompanied by a greater change in mRNA splicing and polyadenylation than in gene expression and they characterise signalling pathways involved in differentiation.
Databáze: OpenAIRE
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