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Converting stem cells to dendritic cells by agonist antibodies from unbiased morphogenic selections.


ABSTRACT: When combinatorial antibody libraries are rendered infectious for eukaryotic cells, the integrated antibody genotype and cellular phenotype become permanently linked and each cell becomes a selection system unto itself. These systems should be ideal for the identification of proteins and pathways that regulate differentiation so long as selection systems can be devised. Here we use a selection system based on the ability of secreted antibodies to alter the morphology of colonies expressing them when grown in soft agar. Importantly, this approach is different from all previous studies in that it used a pure discovery format where unbiased libraries that were not preselected against any known protein were used as probes. As such, the strategy is analogous to classical forward genetic approaches except that it operates directly at the protein level. This approach led to the identification of integrin-binding agonist antibodies that efficiently converted human stem cells to dendritic cells.

SUBMITTER: Yea K 

PROVIDER: S-EPMC3773771 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Converting stem cells to dendritic cells by agonist antibodies from unbiased morphogenic selections.

Yea Kyungmoo K   Zhang Hongkai H   Xie Jia J   Jones Teresa M TM   Yang Guang G   Song Byeong Doo BD   Lerner Richard A RA  

Proceedings of the National Academy of Sciences of the United States of America 20130826 37


When combinatorial antibody libraries are rendered infectious for eukaryotic cells, the integrated antibody genotype and cellular phenotype become permanently linked and each cell becomes a selection system unto itself. These systems should be ideal for the identification of proteins and pathways that regulate differentiation so long as selection systems can be devised. Here we use a selection system based on the ability of secreted antibodies to alter the morphology of colonies expressing them  ...[more]

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