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

Journal Article · · Communications Biology

The intestinal epithelium is replaced weekly by non-quiescent stem cells with kinetics that rely on a rapid loss of stemness and choice for secretory or absorptive lineage differentiation. To determine how the cellular transcriptome and proteome changes during these transitions, we developed a new cell sorting method to purify stem cells, secretory and absorptive progenitor cells, and mature, differentiated cells. Transcriptome analyses revealed that as stem cells transition to the progenitor stage, alternative mRNA splicing and polyadenylation dominate changes in the transcriptome. In contrast, as progenitors differentiate into mature cell types, alterations in gene expression and mRNA levels drive the changes. RNA processing targets mRNAs encoding regulators of cell cycle, RNA regulators, cell adhesion, SUMOylation, and Wnt and Notch signaling. Additionally, global proteome profiling of sorted cell populations 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.

Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE Office of Science (SC); National Institutes of Health (NIH); National Science Foundation (NSF)
Grant/Contract Number:
AC05-76RL01830; T32CA009054; R01CA177651; R01GM090056; R01CA244571; P30CA062203; U54CA217378; 1U01CA227544; R21CA223715; DGE‐1321846
OSTI ID:
1668277
Report Number(s):
PNNL-SA-153928
Journal Information:
Communications Biology, Vol. 3, Issue 1; ISSN 2399-3642
Publisher:
Springer NatureCopyright Statement
Country of Publication:
United States
Language:
English

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Figures / Tables (8)