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Analysis of institutional authors

Peso Ovalle, LuisAuthorFernández-Barral AAuthorLarriba MAuthorGarcia-Olmo DAuthorRojo FAuthorBarbáchano AAuthor

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Article

Vitamin D differentially regulates colon stem cells in patient-derived normal and tumor organoids

Publicated to:FEBS Journal. 287 (1): 53-72 - 2020-01-01 287(1), DOI: 10.1111/febs.14998

Authors: Fernandez-Barral, Asuncion; Costales-Carrer, Alba; Buira, Sandra P; Jung, Peter; Ferrer-Mayorga, Gemma; Larriba, Maria Jesus; Bustamante-Madrid, Pilar; Dominguez, Orlando; Real, Francisco X; Guerra-Pastrian, Laura; Lafarga, Miguel; Garcia-Olmo, Damian; Cantero, Ramon; Del Peso, Luis; Batlle, Eduard; Rojo, Federico; Munoz, Alberto; Barbachan, Antonio

Affiliations

Autonomous Univ Madrid UAM, Inst Invest Biomed Alberto Sols, Dept Biochem, Spanish Natl Res Council CSIC, Madrid, Spain - Author
Autonomous Univ Madrid UAM, Inst Invest Biomed Alberto Sols, Dept Canc Biol, Spanish Natl Res Council CSIC, Madrid, Spain - Author
Biomed Res Networking Ctr Oncol CIBERONC, Madrid, Spain - Author
Biomed Res Networking Ctr Resp Dis CIBERES, Madrid, Spain - Author
Biomedical Research Networking Center on Respiratory Diseases (CIBERES) - Author
Centro Nacional de Investigaciones Oncológicas - Author
German Cancer Research Center - Author
Hospital Universitario La Paz - Author
IdiPAZ, Madrid, Spain - Author
Inst Invest Sanitaria Fdn Jimenez Diaz, Dept Pathol, Madrid, Spain - Author
Inst Invest Sanitaria Fdn Jimenez Diaz, Dept Surg, Madrid, Spain - Author
Inst Res Biomed Barcelona IRB, Barcelona, Spain - Author
Instituto de Investigacion Sanitaria La Fe - Author
IRB Barcelona - Institute for Research in Biomedicine - Author
La Paz Univ Hosp IdiPAZ, Dept Pathol, Madrid, Spain - Author
La Paz Univ Hosp IdiPAZ, Dept Surg, Colorectal Unit, Madrid, Spain - Author
Ludwig-Maximilians-Universität München - Author
Spanish Biomedical Research Network Centre in Oncology (CIBERONC) - Author
Spanish Natl Canc Res Ctr CNIO, Madrid, Spain - Author
Univ Cantabria, IDIVAL, Santander, Spain - Author
Universidad Autónoma de Madrid - Author
Universidad de Cantabria - Author
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Abstract

© 2019 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. Intestine is a major target of vitamin D and several studies indicate an association between vitamin D deficiency and inflammatory bowel diseases (IBD), but also increased colorectal cancer (CRC) risk and mortality. However, the putative effects of 1α,25-dihydroxyvitamin D3 (calcitriol), the active vitamin D metabolite, on human colonic stem cells are unknown. Here we show by immunohistochemistry and RNAscope in situ hybridization that vitamin D receptor (VDR) is unexpectedly expressed in LGR5+ colon stem cells in human tissue and in normal and tumor organoid cultures generated from patient biopsies. Interestingly, normal and tumor organoids respond differentially to calcitriol with profound and contrasting changes in their transcriptomic profiles. In normal organoids, calcitriol upregulates stemness-related genes, such as LGR5, SMOC2, LRIG1, MSI1, PTK7, and MEX3A, and inhibits cell proliferation. In contrast, in tumor organoids calcitriol has little effect on stemness-related genes while it induces a differentiated phenotype, and variably reduces cell proliferation. Concordantly, electron microscopy showed that calcitriol does not affect the blastic undifferentiated cell phenotype in normal organoids but it induces a series of differentiated features in tumor organoids. Our results constitute the first demonstration of a regulatory role of vitamin D on human colon stem cells, indicating a homeostatic effect on colon epithelium with relevant implications in IBD and CRC.

Keywords

colon cancercolon stem cellsorganoidsstemness genesApoptosisCalcitriolCalcium channel agonistsCancer-riskCell proliferationCells, culturedColonColon cancerColon stem cellsColonic neoplasmsD-receptorExpansionExpressionFeaturesHumansInhibitionOrganoidsPathwaysProgressionPromotesReceptors, calcitriolSignatureStem cellsStemness genesVdr protein, humanVitamin d

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal FEBS Journal due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2020, it was in position 72/295, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biochemistry & Molecular Biology.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 3.66. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 4.43 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 16.86 (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-30, the following number of citations:

  • WoS: 69
  • Scopus: 78
  • Europe PMC: 53

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-30:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 116.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 116 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 62.11.
  • The number of mentions on the social network Facebook: 3 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 51 (Altmetric).
  • The number of mentions in news outlets: 2 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://repositorio.uam.es/handle/10486/714828

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Germany.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (FERNANDEZ BARRAL, ASUNCION) and Last Author (BARBACHANO BECERRIL, ANTONIO).