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Efficient generation of lens progenitor cells and lentoid bodies from human embryonic stem cells in chemically defined conditions
Author(s) -
Yang Chunbo,
Yang Ying,
Brennan Lisa,
Bouhassira Eric E.,
Kantorow Marc,
Cvekl Ales
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-157255
Subject(s) - microbiology and biotechnology , embryonic stem cell , induced pluripotent stem cell , biology , stem cell , progenitor cell , crystallin , lens (geology) , zebrafish , cellular differentiation , wnt signaling pathway , immunology , signal transduction , genetics , paleontology , gene
The eye lens is an encapsulated avascular organ whose function is to focus light on the retina. Lens comprises a single progenitor cell lineage in multiple states of differentiation. Disruption of lens function leading to protein aggregation and opacity results in age‐onset cataract. Cataract is a complex disease involving genetic and environmental factors. Here, we report the development of a new 3‐stage system that differentiates human embryonic stem cells (hESCs) into large quantities of lens progenitor‐like cells and differentiated 3‐dimensional lentoid bodies. Inhibition of BMP signaling by noggin triggered differentiation of hESCs toward neuroectoderm. Subsequent reactivation of BMP and activation of FGF signaling stimulated formation of lens progenitor cells marked by the expression of PAX6 andα‐crystallins. The formation of lentoid bodies was most efficient in the presence of FGF2 and Wnt‐3a, yielding ∼1000 lentoid bodies/30‐mm well. Lentoid bodies expressed and accumulated lens‐specific markers including αA‐, αB‐, β‐, and γ‐crystallins, filensin, CP49, and MIP/aquaporin 0. Collectively, these studies identify a novel procedure to generate lens cells from hESCs that can be applied for studies of lens differentiation and cataractogenesis using induced pluripotent stem (iPS) cells derived from various cataract patients.—Yang, C., Yang, Y., Brennan, L., Bouhassira, E. E., Kantorow, M., and Cvekl, A. Efficient generation of lens progenitor cells and lentoid bodies from human embryonic stem cells in chemically defined conditions. FASEB J . 24, 3274–3283 (2010). www.fasebj.org