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Derivation of Ethnically Diverse Human Induced Pluripotent Stem Cell Lines.

ABSTRACT: The human genome with all its ethnic variations contributes to differences in human development, aging, disease, repair, and response to medical treatments and is an exciting area of research and clinical study. The availability of well-characterized ethnically diverse stem cell lines is limited and has not kept pace with other advances in stem cell research. Here we derived xenofree ethnically diverse-human induced pluripotent stem cell (ED-iPSC) lines from fibroblasts obtained from individuals of African American, Hispanic-Latino, Asian, and Caucasian ethnic origin and have characterized the lines under a uniform platform for comparative analysis. Derived ED-iPSC lines are low passage number and evaluated in vivo by teratoma formation and in vitro by high throughput microarray analysis of EB formation and early differentiation for tri-lineage commitment to endoderm, ectoderm and mesoderm. These new xenofree ED-iPSC lines represent a well-characterized valuable resource with potential for use in future research in drug discovery or clinical investigations.

SUBMITTER: Chang EA

PROVIDER: S-EPMC5388175 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Derivation of Ethnically Diverse Human Induced Pluripotent Stem Cell Lines.

Chang Eun Ah EA Tomov Martin L ML Suhr Steven T ST Luo Jiesi J Olmsted Zachary T ZT Paluh Janet L JL Cibelli Jose J

Scientific reports 20151020

The human genome with all its ethnic variations contributes to differences in human development, aging, disease, repair, and response to medical treatments and is an exciting area of research and clinical study. The availability of well-characterized ethnically diverse stem cell lines is limited and has not kept pace with other advances in stem cell research. Here we derived xenofree ethnically diverse-human induced pluripotent stem cell (ED-iPSC) lines from fibroblasts obtained from individuals ...[more]

PMID: 26482195

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Project description:BACKGROUND:The role of brown fat in non-shivering thermogenesis and the discovery of brown fat depots in adult humans has made it the subject of intense research interest. A renewable source of brown adipocyte (BA) progenitors would be highly valuable for research and therapy. Directed differentiation of human pluripotent stem (hPS) cells to white or brown adipocytes is limited by lack of cell purity and scalability. Here we describe an alternative approach involving the identification of clonal self-renewing human embryonic progenitor (hEP) cell lines following partial hPS cell differentiation and selection of scalable clones. METHODS:We screened a diverse panel of hPS cell-derived clonal hEP cell lines for adipocyte markers following growth in adipocyte differentiation medium. The transcriptome of the human hES-derived clonal embryonic progenitor cell lines E3, C4ELS5.1, NP88, and NP110 representing three class of definitive adipocyte progenitors were compared to the relatively non-adipogenic line E85 and adult-derived BAT and SAT-derived cells using gene expression microarrays, RT-qPCR, metabolic analysis and immunocytochemistry. Differentiation conditions were optimized for maximal UCP1 expression. RESULTS:Many of the differentiated hEP cell lines expressed the adipocyte marker, FAPB4, but only a small subset expressed definitive adipocyte markers including brown adipocyte marker, UCP1. Class I cells (i.e., E3) expressed CITED1, ADIPOQ, and C19orf80 but little to no UCP1. Class II (i.e., C4ELS5.1) expressed CITED1 and UCP1 but little ADIPOQ and LIPASIN. Class III (i.e., NP88, NP110) expressed CITED1, ADIPOQ, C19orf80, and UCP1 in a similar manner as fetal BAT-derived (fBAT) cells. Differentiated NP88 and NP110 lines were closest to fBAT cells morphologically in adiponectin and uncoupling protein expression. But they were more metabolically active than fBAT cells, had higher levels of 3-hydroxybutyrate, and lacked expression of fetal/adult marker, COX7A1. The hEP BA progenitor lines were scalable to 17 passages without loss of differentiation capacity and could be readily rederived. CONCLUSIONS:Taken together, these data demonstrate that self-renewing adipocyte progenitor cells can be derived from hES cells and that they are functionally like BAT cells but with unique properties that might be advantageous for basic research and for development of cell-based treatments for metabolic diseases.

Dataset Information

Derivation of Ethnically Diverse Human Induced Pluripotent Stem Cell Lines.

Publications

Derivation of Ethnically Diverse Human Induced Pluripotent Stem Cell Lines.

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