Secretome Analysis of Inductive Signals for BM-MSC Transdifferentiation into Salivary Gland Progenitors.
Secretome Analysis of Inductive Signals for BM-MSC Transdifferentiation into Salivary Gland Progenitors.
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BM-MSC转分化为唾液腺祖细胞诱导信号的分泌组分析。
DOI：
10.3390/ijms21239055
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发表时间：
2020-11-28
影响因子：
5.6
通讯作者：
Cha S
中科院分区：
文献类型：
--
作者：
Mona M;Kobeissy F;Park YJ;Miller R;Saleh W;Koh J;Yoo MJ;Chen S;Cha S
干燥综合征患者的严重口干，或头颈部癌症患者的放射治疗，都会严重损害他们的口腔健康和生活质量。口干症目前的临床治疗仅限于姑息治疗，因为目前还没有经过临床验证的治疗方法。此前，我们的研究表明，小鼠骨髓间充质干细胞(MMSCs)在与原代唾液上皮细胞共培养时，可以分化为唾液前体细胞。随着细胞形态的改变和腺泡细胞标志物如α-淀粉酶、M_3R、水通道蛋白-5和导管细胞标志物细胞角蛋白19的表达，mMSCs表达上调的转录因子被鉴定。在本研究中，我们通过高通量液相色谱-串联质谱仪和系统生物学，进一步探索了条件培养液中导致MMSC重编程的诱导分子。我们的方法根据它们在唾液腺胚胎发生和发育中的假定作用确定了10个差异表达的蛋白质。此外，系统生物学分析还发现了6种候选蛋白，即胰岛素样生长因子结合蛋白-7(IGFBP7)、富含半胱氨酸的血管生成诱导剂61(CyR61)、集聚蛋白(AGRN)、层粘连蛋白、β2(LAMB2)、卵泡抑素样蛋白1(FSTL1)和纤维连接蛋白1(FN1)，它们在MMSC共培养过程中可能起到转分化作用。据我们所知，我们的研究是该领域第一个识别可溶性诱导分子将MMSC转化为跨越谱系边界的唾液祖细胞的研究。
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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影响因子：
24
作者：
Adam, Oliver;Lavall, Daniel;Laufs, Ulrich
通讯作者：
Laufs, Ulrich
影响因子：
--
作者：
Bonnet A;Lagarrigue S;Liaubet L;Robert-Granié C;Sancristobal M;Tosser-Klopp G
通讯作者：
Tosser-Klopp G
DOI：
10.1002/neu.10025
发表时间：
2002-02-05
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Bixby, JL;Baerwald-De la Torre, K;Rüegg, MA
通讯作者：
Rüegg, MA
影响因子：
29.4
作者：
Bachem, MG;Schneider, E;Adler, G
通讯作者：
Adler, G
DOI：
10.15386/cjmed-748
发表时间：
2018-01-01
期刊：
Clujul medical (1957)
影响因子：
--
作者：
Bakhtiari, Sedigheh;Sehatpour, Marziye;Bakhshi, Mahin
通讯作者：
Bakhshi, Mahin