Alberto Muñoz's team has conducted a pioneering study on the effect of vitamin D on colon epithelial stem cells
This work, entitled Vitamin D opposes multilineage cell differentiation induced by Notch inhibition and BMP4 pathway activation in human colon organoids, has been published in the journal Cell Death and Disease. This study describes the establishment of a cell differentiation model in human colon organoids. Stem cells derived from the colon crypt are differentiated into the most common cell types found in the colonic epithelium: enterocytes, responsible for water absorption, and goblet cells, essential for producing mucus to facilitate the passage of feces through the intestinal tract. This model offers valuable opportunities for in-depth studies on the biology and pathologies of the colon.
The Colon Cancer: Organoids, Microenvironment and Vitamin D group, led by Prof. Alberto Muñoz del Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM) CSIC-UAM, have used methodologies such as RNA-seq, Western blot, immunofluorescence, as well as a pioneering ultrastructural analysis by electron microscopy to achieved a holistic and detailed understanding of the prodifferentiation action that Bone Morphogenetic Protein (BMP)-4 and the inhibition of Notch signaling pathway exert on colon crypt stem cells, and characterized the effect of calcitriol (the active vitamin D metabolite) on this process.
This study reveals that calcitriol favors the undifferentiated phenotype of human colon stem cells, thereby preserving their reservoir, which is crucial for the weekly renewal of the colonic epithelium in adult life. On the other hand, in line with the antitumoral effect of vitamin D, the study shows that calcitriol has a cell pro-differentiation effect on colon tumor organoids.
The figure shows electron microscopy images showing how the organoids reliably reproduce the different cell types of the colon crypt.
“This study emphasizes, once again, the importance of maintaining optimal bloodstream vitamin D levels as a preventive measure against colonic epithelial deterioration, often associated with inflammatory bowel disease (ulcerative colitis and Crohn's disease) and antitumoral therapies”, highlights Dr. Pilar Bustamante-Madrid. “Moreover, our work underscores that this differentiation model using patient-derived paired normal and tumor organoids can be very valuable for the identification of antitumoral drugs with minimal side effects” explains Dr. Asunción Fernández-Barral.
This study has been conducted by an interdisciplinary team including researchers from the IIBM (CSIC-UAM), Centro de Investigación Biomédica en Red-Cáncer (CIBERONC), and Instituto de Investigación Sanitaria Hospital Universitario La Paz, (IdiPAZ), in collaboration with oncologists, surgeons, and endoscopists from the same Hospital, as well as researchers from the Centro Nacional de Investigaciones Oncológicas (CNIO), and Universidad de Cantabria-IDIVAL.
The article: Vitamin D opposes multilineage cell differentiation induced by Notch inhibition and BMP4 pathway activation in human colon organoids" can be read HERE.