Efficient generation of lens progenitor cells from cataract patient-specific induced pluripotent stem cells.
The development of a technique to induce the transformation of somatic cells to a pluripotent state via the ectopic expression of defined transcription factors was a transformational event in the field of regenerative medicine. The development of this technique also impacted ophthalmology, as patien...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3293838?pdf=render |
| _version_ | 1811306248912502784 |
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| author | Xiaodi Qiu Jin Yang Tianjin Liu Yongxiang Jiang Qihua Le Yi Lu |
| author_facet | Xiaodi Qiu Jin Yang Tianjin Liu Yongxiang Jiang Qihua Le Yi Lu |
| author_sort | Xiaodi Qiu |
| collection | DOAJ |
| description | The development of a technique to induce the transformation of somatic cells to a pluripotent state via the ectopic expression of defined transcription factors was a transformational event in the field of regenerative medicine. The development of this technique also impacted ophthalmology, as patient-specific induced pluripotent stemcells (iPSCs) may be useful resources for some ophthalmological diseases. The lens is a key refractive element in the eye that focuses images of the visual world onto the retina. To establish a new model for drug screening to treat lens diseases and investigating lens aging and development, we examined whether human lens epithelial cells (HLECs) could be induced into iPSCs and if lens-specific differentiation of these cells could be achieved under defined chemical conditions. We first efficiently reprogrammed HLECs from age-related cataract patients to iPSCs with OCT-4, SOX-2, and KLF-4. The resulting HLEC-derived iPS (HLE-iPS) colonies were indistinguishable from human ES cells with respect to morphology, gene expression, pluripotent marker expression and their ability to generate all embryonic germ-cell layers. Next, we performed a 3-step induction procedure: HLE-iPS cells were differentiated into large numbers of lens progenitor-like cells with defined factors (Noggin, BMP and FGF2), and we determined that these cells expressed lens-specific markers (PAX6, SOX2, SIX3, CRYAB, CRYAA, BFSP1, and MIP). In addition, HLE-iPS-derived lens cells exhibited reduced expression of epithelial mesenchymal transition (EMT) markers compared with human embryonic stem cells (hESCs) and fibroblast-derived iPSCs. Our study describes a highly efficient procedure for generating lens progenitor cells from cataract patient HLEC-derived iPSCs. These patient-derived pluripotent cells provide a valuable model for studying the developmental and molecular biological mechanisms that underlie cell determination in lens development and cataract pathophysiology. |
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| id | doaj.art-4e5b558aff0d44819a1ee81bd8dca87f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T08:41:00Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-4e5b558aff0d44819a1ee81bd8dca87f2022-12-22T02:53:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3261210.1371/journal.pone.0032612Efficient generation of lens progenitor cells from cataract patient-specific induced pluripotent stem cells.Xiaodi QiuJin YangTianjin LiuYongxiang JiangQihua LeYi LuThe development of a technique to induce the transformation of somatic cells to a pluripotent state via the ectopic expression of defined transcription factors was a transformational event in the field of regenerative medicine. The development of this technique also impacted ophthalmology, as patient-specific induced pluripotent stemcells (iPSCs) may be useful resources for some ophthalmological diseases. The lens is a key refractive element in the eye that focuses images of the visual world onto the retina. To establish a new model for drug screening to treat lens diseases and investigating lens aging and development, we examined whether human lens epithelial cells (HLECs) could be induced into iPSCs and if lens-specific differentiation of these cells could be achieved under defined chemical conditions. We first efficiently reprogrammed HLECs from age-related cataract patients to iPSCs with OCT-4, SOX-2, and KLF-4. The resulting HLEC-derived iPS (HLE-iPS) colonies were indistinguishable from human ES cells with respect to morphology, gene expression, pluripotent marker expression and their ability to generate all embryonic germ-cell layers. Next, we performed a 3-step induction procedure: HLE-iPS cells were differentiated into large numbers of lens progenitor-like cells with defined factors (Noggin, BMP and FGF2), and we determined that these cells expressed lens-specific markers (PAX6, SOX2, SIX3, CRYAB, CRYAA, BFSP1, and MIP). In addition, HLE-iPS-derived lens cells exhibited reduced expression of epithelial mesenchymal transition (EMT) markers compared with human embryonic stem cells (hESCs) and fibroblast-derived iPSCs. Our study describes a highly efficient procedure for generating lens progenitor cells from cataract patient HLEC-derived iPSCs. These patient-derived pluripotent cells provide a valuable model for studying the developmental and molecular biological mechanisms that underlie cell determination in lens development and cataract pathophysiology.http://europepmc.org/articles/PMC3293838?pdf=render |
| spellingShingle | Xiaodi Qiu Jin Yang Tianjin Liu Yongxiang Jiang Qihua Le Yi Lu Efficient generation of lens progenitor cells from cataract patient-specific induced pluripotent stem cells. PLoS ONE |
| title | Efficient generation of lens progenitor cells from cataract patient-specific induced pluripotent stem cells. |
| title_full | Efficient generation of lens progenitor cells from cataract patient-specific induced pluripotent stem cells. |
| title_fullStr | Efficient generation of lens progenitor cells from cataract patient-specific induced pluripotent stem cells. |
| title_full_unstemmed | Efficient generation of lens progenitor cells from cataract patient-specific induced pluripotent stem cells. |
| title_short | Efficient generation of lens progenitor cells from cataract patient-specific induced pluripotent stem cells. |
| title_sort | efficient generation of lens progenitor cells from cataract patient specific induced pluripotent stem cells |
| url | http://europepmc.org/articles/PMC3293838?pdf=render |
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