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Induction of salivary gland-like cells from epithelial tissues transdifferentiated from mouse embryonic fibroblasts

Katada, Ryogo ; Tanaka, Junichi ; Takamatsu, Koki ; Hata, Kenji ; Yasuhara, Rika ; Ohnuma, Shintaro ; Takakura, Ikuko ; Nishimura, Riko ; Shirota, Tatsuo ; Mishima, Kenji

Biochemical and biophysical research communications, 2022-01, Vol.586, p.55-62 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Induction of salivary gland-like cells from epithelial tissues transdifferentiated from mouse embryonic fibroblasts
Autor: Katada, Ryogo ; Tanaka, Junichi ; Takamatsu, Koki ; Hata, Kenji ; Yasuhara, Rika ; Ohnuma, Shintaro ; Takakura, Ikuko ; Nishimura, Riko ; Shirota, Tatsuo ; Mishima, Kenji
Assuntos: Acinar Cells - cytology ; Acinar Cells - metabolism ; Adenoviridae - genetics ; Adenoviridae - metabolism ; Animals ; Aquaporin 5 - genetics ; Aquaporin 5 - metabolism ; Biomarkers - metabolism ; Cadherins - genetics ; Cadherins - metabolism ; Cell Transdifferentiation - genetics ; Cell- and Tissue-Based Therapy - methods ; Dry mouth ; Embryo, Mammalian ; Fibroblasts - cytology ; Fibroblasts - metabolism ; Forkhead Transcription Factors - genetics ; Forkhead Transcription Factors - metabolism ; Gene Expression ; Genetic Vectors - chemistry ; Genetic Vectors - metabolism ; Keratin-14 - genetics ; Keratin-14 - metabolism ; Keratin-5 - genetics ; Keratin-5 - metabolism ; Mice ; Mouse embryonic fibroblasts ; Proto-Oncogene Proteins c-myc - genetics ; Proto-Oncogene Proteins c-myc - metabolism ; Salivary glands ; Salivary Glands - cytology ; Salivary Glands - metabolism ; SOX9 Transcription Factor - genetics ; SOX9 Transcription Factor - metabolism ; Spheroids, Cellular - cytology ; Spheroids, Cellular - metabolism ; Trans-Activators - genetics ; Trans-Activators - metabolism ; Transcription Factor AP-2 - genetics ; Transcription Factor AP-2 - metabolism ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Transdifferentiation
É parte de: Biochemical and biophysical research communications, 2022-01, Vol.586, p.55-62
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Descrição: Salivary gland hypofunction due to radiation therapy for head and neck cancer or Sjögren syndrome may cause various oral diseases, which can lead to a decline in the quality of life. Cell therapy using salivary gland stem cells is a promising method for restoring hypofunction. Herein, we show that salivary gland-like cells can be induced from epithelial tissues that were transdifferentiated from mouse embryonic fibroblasts (MEFs). We introduced four genes, Dnp63a, Tfap2a, Grhl2, and Myc (PTMG) that are known to transdifferentiate fibroblasts into oral mucosa-like epithelium in vivo into MEFs. MEFs overexpressing these genes showed epithelial cell characteristics, such as cobblestone appearance and E-cadherin positivity, and formed oral epithelial-like tissue under air–liquid interface culture conditions. The epithelial sheet detached from the culture dish was infected with adenoviruses encoding Sox9 and Foxc1, which we previously identified as essential factors to induce salivary gland formation. The cells detached from the cell sheet formed spheres 10 days after infection and showed a branching morphology. The spheres expressed genes encoding basal/myoepithelial markers, cytokeratin 5, cytokeratin 14, acinar cell marker, aquaporin 5, and the myoepithelial marker α-smooth muscle actin. The dissociated cells of these primary spheres had the ability to form secondary spheres. Taken together, our results provide a new strategy for cell therapy of salivary glands and hold implications in treating patients with dry mouth. •The PTMG-derived epithelial sheet can differentiate into salivary gland-like cells after infection with Ad-SOX9 and Ad-Foxc1.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Induction of salivary gland-like cells from epithelial tissues transdifferentiated from mouse embryonic fibroblasts

Katada, Ryogo ; Tanaka, Junichi ; Takamatsu, Koki ; Hata, Kenji ; Yasuhara, Rika ; Ohnuma, Shintaro ; Takakura, Ikuko ; Nishimura, Riko ; Shirota, Tatsuo ; Mishima, Kenji

United States: Elsevier Inc

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