Elucidation of HHEX in pancreatic endoderm differentiation using a human iPSC differentiation model
Abstract For pluripotent stem cell (PSC)-based regenerative therapy against diabetes, the differentiation efficiency to pancreatic lineage cells needs to be improved based on the mechanistic understanding of pancreatic differentiation. Here, we aimed to elucidate the molecular mechanisms underlying...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-35875-1 |
| _version_ | 1797811579269414912 |
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| author | Ryo Ito Azuma Kimura Yurie Hirose Yu Hatano Atsushi Mima Shin-Ichi Mae Yamato Keidai Toshihiro Nakamura Junji Fujikura Yohei Nishi Akira Ohta Taro Toyoda Nobuya Inagaki Kenji Osafune |
| author_facet | Ryo Ito Azuma Kimura Yurie Hirose Yu Hatano Atsushi Mima Shin-Ichi Mae Yamato Keidai Toshihiro Nakamura Junji Fujikura Yohei Nishi Akira Ohta Taro Toyoda Nobuya Inagaki Kenji Osafune |
| author_sort | Ryo Ito |
| collection | DOAJ |
| description | Abstract For pluripotent stem cell (PSC)-based regenerative therapy against diabetes, the differentiation efficiency to pancreatic lineage cells needs to be improved based on the mechanistic understanding of pancreatic differentiation. Here, we aimed to elucidate the molecular mechanisms underlying pancreatic endoderm differentiation by searching for factors that regulate a crucial pancreatic endoderm marker gene, NKX6.1. Unbiasedly screening an siRNA knockdown library, we identified a candidate transcription factor, HHEX. HHEX knockdown suppressed the expression of another pancreatic endoderm marker gene, PTF1A, as well as NKX6.1, independently of PDX1, a known regulator of NKX6.1 expression. In contrast, the overexpression of HHEX upregulated the expressions of NKX6.1 and PTF1A. RNA-seq analysis showed decreased expressions of several genes related to pancreatic development, such as NKX6.1, PTF1A, ONECUT1 and ONECUT3, in HHEX knockdown pancreatic endoderm. These results suggest that HHEX plays a key role in pancreatic endoderm differentiation. |
| first_indexed | 2024-03-13T07:25:50Z |
| format | Article |
| id | doaj.art-df2cb19d80214e9ca8bdf82af4846cfd |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T07:25:50Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-df2cb19d80214e9ca8bdf82af4846cfd2023-06-04T11:25:11ZengNature PortfolioScientific Reports2045-23222023-05-0113111210.1038/s41598-023-35875-1Elucidation of HHEX in pancreatic endoderm differentiation using a human iPSC differentiation modelRyo Ito0Azuma Kimura1Yurie Hirose2Yu Hatano3Atsushi Mima4Shin-Ichi Mae5Yamato Keidai6Toshihiro Nakamura7Junji Fujikura8Yohei Nishi9Akira Ohta10Taro Toyoda11Nobuya Inagaki12Kenji Osafune13Center for iPS Cell Research and Application (CiRA), Kyoto UniversityCenter for iPS Cell Research and Application (CiRA), Kyoto UniversityCenter for iPS Cell Research and Application (CiRA), Kyoto UniversityCenter for iPS Cell Research and Application (CiRA), Kyoto UniversityCenter for iPS Cell Research and Application (CiRA), Kyoto UniversityCenter for iPS Cell Research and Application (CiRA), Kyoto UniversityDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto UniversityDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto UniversityDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto UniversityCenter for iPS Cell Research and Application (CiRA), Kyoto UniversityCenter for iPS Cell Research and Application (CiRA), Kyoto UniversityCenter for iPS Cell Research and Application (CiRA), Kyoto UniversityDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto UniversityCenter for iPS Cell Research and Application (CiRA), Kyoto UniversityAbstract For pluripotent stem cell (PSC)-based regenerative therapy against diabetes, the differentiation efficiency to pancreatic lineage cells needs to be improved based on the mechanistic understanding of pancreatic differentiation. Here, we aimed to elucidate the molecular mechanisms underlying pancreatic endoderm differentiation by searching for factors that regulate a crucial pancreatic endoderm marker gene, NKX6.1. Unbiasedly screening an siRNA knockdown library, we identified a candidate transcription factor, HHEX. HHEX knockdown suppressed the expression of another pancreatic endoderm marker gene, PTF1A, as well as NKX6.1, independently of PDX1, a known regulator of NKX6.1 expression. In contrast, the overexpression of HHEX upregulated the expressions of NKX6.1 and PTF1A. RNA-seq analysis showed decreased expressions of several genes related to pancreatic development, such as NKX6.1, PTF1A, ONECUT1 and ONECUT3, in HHEX knockdown pancreatic endoderm. These results suggest that HHEX plays a key role in pancreatic endoderm differentiation.https://doi.org/10.1038/s41598-023-35875-1 |
| spellingShingle | Ryo Ito Azuma Kimura Yurie Hirose Yu Hatano Atsushi Mima Shin-Ichi Mae Yamato Keidai Toshihiro Nakamura Junji Fujikura Yohei Nishi Akira Ohta Taro Toyoda Nobuya Inagaki Kenji Osafune Elucidation of HHEX in pancreatic endoderm differentiation using a human iPSC differentiation model Scientific Reports |
| title | Elucidation of HHEX in pancreatic endoderm differentiation using a human iPSC differentiation model |
| title_full | Elucidation of HHEX in pancreatic endoderm differentiation using a human iPSC differentiation model |
| title_fullStr | Elucidation of HHEX in pancreatic endoderm differentiation using a human iPSC differentiation model |
| title_full_unstemmed | Elucidation of HHEX in pancreatic endoderm differentiation using a human iPSC differentiation model |
| title_short | Elucidation of HHEX in pancreatic endoderm differentiation using a human iPSC differentiation model |
| title_sort | elucidation of hhex in pancreatic endoderm differentiation using a human ipsc differentiation model |
| url | https://doi.org/10.1038/s41598-023-35875-1 |
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