title: Efficient induction of pluripotent stem cells from menstrual blood.
abstract: The technology to reprogram human somatic cells back to pluripotency allows the production of patient-specific induced pluripotent stem cells (iPSCs) and holds a great promise for regenerative medicine. Choosing the most suitable cell type for induction and reducing the risk of viral transgene activation, especially oncogene activation, are important for iPSC research. To date, human dermal fibroblasts (HDFs) are the most frequent cell source used for iPSC generation, but they have several limitations. An invasive skin biopsy must be performed to obtain HDFs, and HDFs must be cultured for a prolonged period before they can be used for experiments. Thus, in an effort to develop a suitable source for iPSC studies to avoid the limitations mentioned above, we have here identified stromal cells derived from menstrual blood (MenSCs) as suitable candidates. In the present study, we found that MenSCs can be reprogrammed to pluripotent status by doxycycline-inducible lentiviral transduction of OCT4, SOX2, and KLF4. Additionally, we found that MenSCs have a significantly higher reprogramming efficiency than HDFs. The combination of OCT4 and SOX2 is sufficient to reprogram MenSCs into iPSCs without the use of c-MYC or KLF4. The resulting MenSC-iPSCs showed the same characteristics as human embryonic stem cells with regard to morphology, pluripotent markers, gene expression, and the epigenetic status of pluripotent-cell-specific genes. These cells were able to differentiate into various cell types of all 3 germ layers both in vitro and in vivo. Therefore, MenSCs may be a preferred candidate for generation of iPSCs.
authors.affiliation: Stem Cell Research Center and Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaoni
authors.initials: X
authors.lastname: Li
authors.forename: Hongxi
authors.initials: H
authors.lastname: Zhao
authors.forename: Ruopeng
authors.initials: R
authors.lastname: Feng
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Dapeng
authors.initials: D
authors.lastname: Tai
authors.forename: Guangyu
authors.initials: G
authors.lastname: An
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wen
authors.forename: Jichun
authors.initials: J
authors.lastname: Tan
mesh_terms: D000328:Adult; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D019175:DNA Methylation; D005260:Female; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D059785:Karyotype; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008597:Menstrual Cycle / Q000097:blood*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors