The development of a technique to induce the transformation of somatic cells to a pluripotent state via the ectopic\r\nexpression of defined transcription factors was a transformational event in the field of regenerative medicine. The\r\ndevelopment of this technique also impacted ophthalmology, as patient-specific induced pluripotent stemcells (iPSCs) may\r\nbe useful resources for some ophthalmological diseases. The lens is a key refractive element in the eye that focuses images\r\nof the visual world onto the retina. To establish a new model for drug screening to treat lens diseases and investigating lens\r\naging and development, we examined whether human lens epithelial cells (HLECs) could be induced into iPSCs and if lensspecific\r\ndifferentiation of these cells could be achieved under defined chemical conditions. We first efficiently\r\nreprogrammed HLECs from age-related cataract patients to iPSCs with OCT-4, SOX-2, and KLF-4. The resulting HLECderived\r\niPS (HLE-iPS) colonies were indistinguishable from human ES cells with respect to morphology, gene expression,\r\npluripotent marker expression and their ability to generate all embryonic germ-cell layers. Next, we performed a 3-step\r\ninduction procedure: HLE-iPS cells were differentiated into large numbers of lens progenitor-like cells with defined factors\r\n(Noggin, BMP and FGF2), and we determined that these cells expressed lens-specific markers (PAX6, SOX2, SIX3, CRYAB,\r\nCRYAA, BFSP1, and MIP). In addition, HLE-iPS-derived lens cells exhibited reduced expression of epithelial mesenchymal\r\ntransition (EMT) markers compared with human embryonic stem cells (hESCs) and fibroblast-derived iPSCs. Our study\r\ndescribes a highly efficient procedure for generating lens progenitor cells from cataract patient HLEC-derived iPSCs. These\r\npatient-derived pluripotent cells provide a valuable model for studying the developmental and molecular biological\r\nmechanisms that underlie cell determination in lens development and cataract pathophysiology.
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