학술논문

SRSF1 governs progenitor-specific alternative splicing to maintain adult epithelial tissue homeostasis and renewal
Document Type
article
Source
Developmental Cell. 57(5)
Subject
Biochemistry and Cell Biology
Biological Sciences
Genetics
Stem Cell Research - Nonembryonic - Non-Human
Stem Cell Research
Underpinning research
1.1 Normal biological development and functioning
Generic health relevance
Alternative Splicing
Animals
Epithelium
Homeostasis
Mice
RNA Splicing
Serine-Arginine Splicing Factors
alternative splicing
incisor
intestine
mouse
progenitor
splicing factor
tissue homeostasis
tissue renewal
Medical and Health Sciences
Developmental Biology
Biochemistry and cell biology
Language
Abstract
Alternative splicing generates distinct mRNA variants and is essential for development, homeostasis, and renewal. Proteins of the serine/arginine (SR)-rich splicing factor family are major splicing regulators that are broadly required for organ development as well as cell and organism viability. However, how these proteins support adult organ function remains largely unknown. Here, we used the continuously growing mouse incisor as a model to dissect the functions of the prototypical SR family protein SRSF1 during tissue homeostasis and renewal. We identified an SRSF1-governed alternative splicing network that is specifically required for dental proliferation and survival of progenitors but dispensable for the viability of differentiated cells. We also observed a similar progenitor-specific role of SRSF1 in the small intestinal epithelium, indicating a conserved function of SRSF1 across adult epithelial tissues. Thus, our findings define a regulatory mechanism by which SRSF1 specifically controls progenitor-specific alternative splicing events to support adult tissue homeostasis and renewal.