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Single Cell RNA Sequencing of Papillary Cancer Mesenchymal Stem/Stromal Cells Reveals a Transcriptional Profile That Supports a Role for These Cells in Cancer Progression

Lookup NU author(s): Danny Jandu, Artida Bajrami, Dr Rachel QueenORCiD, Matthew TeasdaleORCiD, Raf Hussain, Dr Jonathan Coxhead, Dr Annette Meeson

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Papillary thyroid cancer (PTC) contains mesenchymal stem/stromal cells (MSCs), but their contribution to PTC progression is not clear. In this study, we compared the transcriptional signatures of normal thyroid (NT) and PTC-derived MSCs with the aim of determining if these have distinct transcriptomes that might influence PTC progression. We used flow cytometry in combination with a panel of MSC clusters of differentiation (CD) markers and showed that both thyroid MSC populations expressed MSC markers and lacked expression of markers not normally expressed by MSCs. In addition, we determined that both MSC populations could differentiate to adipocytes and osteocytes. Analysis of single cell RNA sequencing data from both MSC populations revealed, regardless of tissue of origin, that both contained similar numbers of subpopulations. Cluster analysis revealed similarity in expression of both MSC populations for stromal markers, the vascular marker VEGFA and the smooth muscle marker CALD1, while smaller subpopulations expressed markers of more lineage-committed thyroid cells. PTC MSCs also showed upregulated expression of 28 genes, many of which are known to be involved in epithelial–mesenchymal transition (EMT) and/or disease progression in several types of cancers, including but not limited to breast cancer, gastric cancer, cervical carcinoma, bladder cancer and thyroid cancer. This included several members of the S100 and IGFBP gene families. Taken together, these data support a role for PTC MSCs in PTC progression.


Publication metadata

Author(s): Jandu D, Latar N, Bajrami A, Queen R, Hasoon M, Teasdale M, Hussain R, Coxhead J, Aspinall S, Meeson A

Publication type: Article

Publication status: Published

Journal: International Journal of Molecular Sciences

Year: 2025

Volume: 26

Issue: 10

Pages: 4957

Online publication date: 21/05/2025

Acceptance date: 15/05/2025

Date deposited: 08/07/2025

ISSN (electronic): 1422-0067

Publisher: MDPI

URL: https://doi.org/10.3390/ijms26104957

DOI: 10.3390/ijms26104957

Data Access Statement: The data presented in this study are available on request from the corresponding author


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Funding

Funder referenceFunder name
Oracle Cancer Trust grant number NU-000109.

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