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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...

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Autores principales: Mona, Mahmoud, Kobeissy, Firas, Park, Yun-Jong, Miller, Rehae, Saleh, Wafaa, Koh, Jin, Yoo, Mi-Jeong, Chen, Sixue, Cha, Seunghee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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