Journal article
BVES Regulates Intestinal Stem Cell Programs and Intestinal Crypt Viability after Radiation
Stem cells (Dayton, Ohio), Vol.34(6), pp.1626-1636
06/2016
DOI: 10.1002/stem.2307
PMCID: PMC4893006
PMID: 26891025
Abstract
Blood vessel epicardial substance (BVES/Popdc1) is a junctional-associated transmembrane protein that is underexpressed in a number of malignancies and regulates epithelial-to-mesenchymal transition. We previously identified a role for BVES in regulation of the Wnt pathway, a modulator of intestinal stem cell programs, but its role in small intestinal (SI) biology remains unexplored. We hypothesized that BVES influences intestinal stem cell programs and is critical to SI homeostasis after radiation injury. At baseline, Bves(-/-) mice demonstrated increased crypt height, as well as elevated proliferation and expression of the stem cell marker Lgr5 compared to wild-type (WT) mice. Intercross with Lgr5-EGFP reporter mice confirmed expansion of the stem cell compartment in Bves(-/-) mice. To examine stem cell function after BVES deletion, we used ex vivo 3D-enteroid cultures. Bves(-/-) enteroids demonstrated increased stemness compared to WT, when examining parameters such as plating efficiency, stem spheroid formation, and retention of peripheral cystic structures. Furthermore, we observed increased proliferation, expression of crypt-base columnar "CBC" and "+4" stem cell markers, amplified Wnt signaling, and responsiveness to Wnt activation in the Bves(-/-) enteroids. Bves expression was downregulated after radiation in WT mice. Moreover, after radiation, Bves(-/-) mice demonstrated significantly greater SI crypt viability, proliferation, and amplified Wnt signaling in comparison to WT mice. Bves(-/-) mice also demonstrated elevations in Lgr5 and Ascl2 expression, and putative damage-responsive stem cell populations marked by Bmi1 and TERT. Therefore, BVES is a key regulator of intestinal stem cell programs and mucosal homeostasis. Stem Cells 2016;34:1626-1636.
Details
- Title: Subtitle
- BVES Regulates Intestinal Stem Cell Programs and Intestinal Crypt Viability after Radiation
- Creators
- Vishruth K Reddy - Vanderbilt University Medical CenterSarah P Short - Vanderbilt University Medical CenterCaitlyn W Barrett - University of PittsburghMukul K Mittal - Vanderbilt University Medical CenterCody E Keating - Vanderbilt University Medical CenterJoshua J Thompson - Vanderbilt University Medical CenterElizabeth I Harris - Vanderbilt University Medical CenterFrank Revetta - Vanderbilt University Medical CenterDavid M Bader - Vanderbilt University Medical CenterThomas Brand - Imperial College LondonM Kay Washington - Vanderbilt University Medical CenterChristopher S Williams - Vanderbilt University Medical Center
- Resource Type
- Journal article
- Publication Details
- Stem cells (Dayton, Ohio), Vol.34(6), pp.1626-1636
- DOI
- 10.1002/stem.2307
- PMID
- 26891025
- PMCID
- PMC4893006
- ISSN
- 1066-5099
- eISSN
- 1549-4918
- Grant note
- F30 DK103498 / NIDDK NIH HHS P01 CA077839 / NCI NIH HHS P50 CA095103 / NCI NIH HHS R01 DK099204 / NIDDK NIH HHS P30 DK058404 / NIDDK NIH HHS L30 DK076274 / NIDDK NIH HHS MR/J010383/1 / Medical Research Council K08 DK080221 / NIDDK NIH HHS UL1 TR000445 / NCATS NIH HHS I01 BX001426 / BLRD VA P30 CA068485 / NCI NIH HHS T32 GM007347 / NIGMS NIH HHS S10 OD021630 / NIH HHS
- Language
- English
- Date published
- 06/2016
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984420844902771
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