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Secretome Analysis of Inductive Signals for BM-MSC Transdifferentiation into Salivary Gland Progenitors
Severe dry mouth in patients with Sjögren’s Syndrome, or radiation therapy for patients with head and neck cancer, significantly compromises their oral health and quality of life. The current clinical management of xerostomia is limited to palliative care as there are no clinically-proven treatments...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730006/ https://www.ncbi.nlm.nih.gov/pubmed/33260559 http://dx.doi.org/10.3390/ijms21239055 |
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author | Mona, Mahmoud Kobeissy, Firas Park, Yun-Jong Miller, Rehae Saleh, Wafaa Koh, Jin Yoo, Mi-Jeong Chen, Sixue Cha, Seunghee |
author_facet | Mona, Mahmoud Kobeissy, Firas Park, Yun-Jong Miller, Rehae Saleh, Wafaa Koh, Jin Yoo, Mi-Jeong Chen, Sixue Cha, Seunghee |
author_sort | Mona, Mahmoud |
collection | PubMed |
description | Severe dry mouth in patients with Sjögren’s Syndrome, or radiation therapy for patients with head and neck cancer, significantly compromises their oral health and quality of life. The current clinical management of xerostomia is limited to palliative care as there are no clinically-proven treatments available. Previously, our studies demonstrated that mouse bone marrow-derived mesenchymal stem cells (mMSCs) can differentiate into salivary progenitors when co-cultured with primary salivary epithelial cells. Transcription factors that were upregulated in co-cultured mMSCs were identified concomitantly with morphological changes and the expression of acinar cell markers, such as α-amylase (AMY1), muscarinic-type-3-receptor(M3R), aquaporin-5(AQP5), and a ductal cell marker known as cytokeratin 19(CK19). In the present study, we further explored inductive molecules in the conditioned media that led to mMSC reprogramming by high-throughput liquid chromatography with tandem mass spectrometry and systems biology. Our approach identified ten differentially expressed proteins based on their putative roles in salivary gland embryogenesis and development. Additionally, systems biology analysis revealed six candidate proteins, namely insulin-like growth factor binding protein-7 (IGFBP7), cysteine-rich, angiogenetic inducer, 61(CYR61), agrin(AGRN), laminin, beta 2 (LAMB2), follistatin-like 1(FSTL1), and fibronectin 1(FN1), for their potential contribution to mMSC transdifferentiation during co-culture. To our knowledge, our study is the first in the field to identify soluble inductive molecules that drive mMSC into salivary progenitors, which crosses lineage boundaries. |
format | Online Article Text |
id | pubmed-7730006 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77300062020-12-12 Secretome Analysis of Inductive Signals for BM-MSC Transdifferentiation into Salivary Gland Progenitors Mona, Mahmoud Kobeissy, Firas Park, Yun-Jong Miller, Rehae Saleh, Wafaa Koh, Jin Yoo, Mi-Jeong Chen, Sixue Cha, Seunghee Int J Mol Sci Article Severe dry mouth in patients with Sjögren’s Syndrome, or radiation therapy for patients with head and neck cancer, significantly compromises their oral health and quality of life. The current clinical management of xerostomia is limited to palliative care as there are no clinically-proven treatments available. Previously, our studies demonstrated that mouse bone marrow-derived mesenchymal stem cells (mMSCs) can differentiate into salivary progenitors when co-cultured with primary salivary epithelial cells. Transcription factors that were upregulated in co-cultured mMSCs were identified concomitantly with morphological changes and the expression of acinar cell markers, such as α-amylase (AMY1), muscarinic-type-3-receptor(M3R), aquaporin-5(AQP5), and a ductal cell marker known as cytokeratin 19(CK19). In the present study, we further explored inductive molecules in the conditioned media that led to mMSC reprogramming by high-throughput liquid chromatography with tandem mass spectrometry and systems biology. Our approach identified ten differentially expressed proteins based on their putative roles in salivary gland embryogenesis and development. Additionally, systems biology analysis revealed six candidate proteins, namely insulin-like growth factor binding protein-7 (IGFBP7), cysteine-rich, angiogenetic inducer, 61(CYR61), agrin(AGRN), laminin, beta 2 (LAMB2), follistatin-like 1(FSTL1), and fibronectin 1(FN1), for their potential contribution to mMSC transdifferentiation during co-culture. To our knowledge, our study is the first in the field to identify soluble inductive molecules that drive mMSC into salivary progenitors, which crosses lineage boundaries. MDPI 2020-11-28 /pmc/articles/PMC7730006/ /pubmed/33260559 http://dx.doi.org/10.3390/ijms21239055 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mona, Mahmoud Kobeissy, Firas Park, Yun-Jong Miller, Rehae Saleh, Wafaa Koh, Jin Yoo, Mi-Jeong Chen, Sixue Cha, Seunghee Secretome Analysis of Inductive Signals for BM-MSC Transdifferentiation into Salivary Gland Progenitors |
title | Secretome Analysis of Inductive Signals for BM-MSC Transdifferentiation into Salivary Gland Progenitors |
title_full | Secretome Analysis of Inductive Signals for BM-MSC Transdifferentiation into Salivary Gland Progenitors |
title_fullStr | Secretome Analysis of Inductive Signals for BM-MSC Transdifferentiation into Salivary Gland Progenitors |
title_full_unstemmed | Secretome Analysis of Inductive Signals for BM-MSC Transdifferentiation into Salivary Gland Progenitors |
title_short | Secretome Analysis of Inductive Signals for BM-MSC Transdifferentiation into Salivary Gland Progenitors |
title_sort | secretome analysis of inductive signals for bm-msc transdifferentiation into salivary gland progenitors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730006/ https://www.ncbi.nlm.nih.gov/pubmed/33260559 http://dx.doi.org/10.3390/ijms21239055 |
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