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We thank Francisca Molina-Jimenez from the Microscopy Unit of the Instituto Investigacion de la Princesa (IISP) for technical assistance with confocal microscopy, and Manuel Gomez for English corrections. We also thank Alejandra Rosell from HUP Pathology Department for acquisition of samples, Marc Elosua Bayes for quality control of spatial transcriptomic data, and CNIC bioinformatic unit, especially to Carlos Torroja for single-cell analysis support. We also warmly thank all the participants included in the study for their selfless participation. This work was supported by the following grants: Proyectos de Investigacion en Salud PI19/00584, PI22/01404, and PMP22/00021 (funded by Instituto de Salud Carlos III), iTIRONET- P2022/BMD7379 (funded by Comunidad de Madrid), Research project IPI/2022/N5 (funded by Sociedad de Endocrinologia, Nutricion y Diabetes de la Comunidad de Madrid-SENDIMAD) and co-financed by FEDER funds to M.M. and R.M.H., as well as Contratos Predoctorales de Formacion en Investigacion en Salud (FI20/00035 and FI23/00052) grants to P.S.G. and N.S.B. The funders had no role in study design, data collection, data analysis, interpretation or writing of the report.

Analysis of institutional authors

Martinez-Hernandez, RebecaCorresponding Author

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February 19, 2025
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Unraveling the molecular architecture of autoimmune thyroid diseases at spatial resolution

Publicated to:Nature Communications. 15 (1): 5895- - 2024-07-13 15(1), DOI: 10.1038/s41467-024-50192-5

Authors: Martinez-Hernandez, Rebeca; de la Blanca, Nuria Sanchez; Sacristan-Gomez, Pablo; Serrano-Somavilla, Ana; De Nova, Jose Luis Munoz; Cabo, Fatima Sanchez; Heyn, Holger; Sampedro-Nunez, Miguel; Marazuela, Monica

Affiliations

Ctr Invest Biomed Red Enfermedades Raras CIBERER G, Madrid, Spain - Author
Ctr Nacl Anal Genom CNAG, Barcelona, Spain - Author
Ctr Nacl Invest Cardiovasc CN, Bioinformat Unit, Madrid, Spain - Author
Univ Autonoma Madrid, Hosp Univ Princesa, Dept Endocrinol & Nutr, Inst Invest Sanitaria Princesa, Madrid, Spain - Author
Univ Autonoma Madrid, Hosp Univ Princesa, Dept Gen & Digest Surg, Inst Invest Sanitaria Princesa, Madrid, Spain - Author
Univ Barcelona UB, Barcelona, Spain - Author
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Abstract

Autoimmune thyroid diseases (AITD) such as Graves' disease (GD) or Hashimoto's thyroiditis (HT) are organ-specific diseases that involve complex interactions between distinct components of thyroid tissue. Here, we use spatial transcriptomics to explore the molecular architecture, heterogeneity and location of different cells present in the thyroid tissue, including thyroid follicular cells (TFCs), stromal cells such as fibroblasts, endothelial cells, and thyroid infiltrating lymphocytes. We identify damaged antigen-presenting TFCs with upregulated CD74 and MIF expression in thyroid samples from AITD patients. Furthermore, we discern two main fibroblast subpopulations in the connective tissue including ADIRF+ myofibroblasts, mainly enriched in GD, and inflammatory fibroblasts, enriched in HT patients. We also demonstrate an increase of fenestrated PLVAP+ vessels in AITD, especially in GD. Our data unveil stromal and thyroid epithelial cell subpopulations that could play a role in the pathogenesis of AITD. Autoimmune thyroid diseases (AITD) are complex conditions involving multiple cellular components of the thyroid tissue. In this study, the authors use spatial transcriptomics data to examine thyroid tissue, identifying distinct subsets of damaged thyroid follicular cells, myofibroblasts and capillaries in AITD.

Keywords

AngiogenesisAntigens, differentiation, b-lymphocyteCellEndothelial cellsExpressionFemaleFibroblastsGraves diseaseHashimoto diseaseHashimotos-thyroiditisHistocompatibility antigens class iiHumansIntramolecular oxidoreductasesInvariant chainMacrophage migration-inhibitory factorsMif protein, humanMif receptorMyofibroblastsPathogenesiProliferationStromal cellsThyrocytesThyroid epithelial cellsThyroid glandTranscriptome

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Nature Communications 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, 2024 there are still no calculated indicators, but in 2023, it was in position 10/135, thus managing to position itself as a Q1 (Primer Cuartil), in the category Multidisciplinary Sciences. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-10-05:

  • WoS: 2
  • Scopus: 2
  • Europe PMC: 3

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 2025-10-05:

  • 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: 21.
  • 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: 18 (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: 11.15.
  • The number of mentions on the social network X (formerly Twitter): 17 (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.

Leadership analysis of institutional authors

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 (Martínez Hernández, Rebeca) .

the author responsible for correspondence tasks has been Martínez Hernández, Rebeca.