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          Institute: MPI für molekulare Biomedizin     Collection: Yearbook 2013     Display Documents

ID: 648344.0, MPI für molekulare Biomedizin / Yearbook 2013
Increased reprogramming capacity of mouse liver progenitor cells, compared with differentiated liver cells, requires the BAF complex
Authors:Kleger, A.; Mahaddalkar, P. U.; Katz, S. F.; Lechel, A.; Joo, J. Y.; Loya, K.; Lin, Q.; Hartmann, D.; Liebau, S.; Kraus, J. M.; Cantz, T.; Kestler, H. A.; Zaehres, H.; Scholer, H.; Rudolph, K. L.
Date of Publication (YYYY-MM-DD):2012-04
Title of Journal:Gastroenterology
Issue / Number:4
Start Page:907
End Page:917
Review Status:Internal review
Audience:Not Specified
Abstract / Description:BACKGROUND & AIMS: Ectopic expression of certain transcription factors can reprogram somatic cells to a pluripotent state. Hematopoietic and muscle stem cells can be more efficiently reprogrammed than differentiated blood or muscle cells, yet similar findings have not been shown in other primary organ systems. Moreover, molecular characteristics of the cellular hierarchy of tissues that influence reprogramming capacities need to be delineated. We analyzed the effect of differentiation stage of freshly isolated, mouse liver cells on the reprogramming efficiency. METHODS: Liver progenitor cell (LPC)-enriched cell fractions were isolated from adult (6-8 wk) and fetal (embryonic day 14.5) livers of mice and reprogrammed to become induced pluripotent stem (iPS) cells. Different transcription factors were expressed in liver cells, and markers of pluripotency were examined, along with the ability of iPS cells to differentiate, in vitro and in vivo, into different germ layers. RESULTS: Fetal and adult LPCs had significantly greater reprogramming efficiency after transduction with 3 or 4 reprogramming factors. Transduction efficiency-corrected reprogramming rates of fetal LPCs were 275-fold higher, compared with unsorted fetal liver cells, when 3 reprogramming factors were transduced. The increased reprogramming efficiency of LPCs, compared with differentiated liver cells, occurred independently of proliferation rates, but was associated with endogenous expression of reprogramming factors (Klf4 and c-Myc) and BAF (Brg1/Brm associated factor)-complex members Baf155 and Brg1, which mediate epigenetic changes during reprogramming. Knockdown of BAF complex members negated the increased reprogramming efficiency of LPCs, compared with non-LPCs. CONCLUSIONS: LPCs have intrinsic, cell proliferation-independent characteristics resulting in an increased reprogramming capacity compared to differentiated liver cells.
Free Keywords:Animals; Biological Markers/metabolism; *Cell Differentiation; Cell Proliferation; Cells, Cultured; DNA Helicases/genetics/*metabolism; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Genotype; Hepatocytes/*metabolism; Induced Pluripotent Stem Cells/*metabolism; Kruppel-Like Transcription Factors/metabolism; Liver/embryology/*metabolism; Mice; Nuclear Proteins/genetics/*metabolism; Phenotype; Proto-Oncogene Proteins c-myc/metabolism; RNA Interference; Time Factors; Transcription Factors/genetics/*metabolism; Transduction, Genetic; Transfection
External Publication Status:published
Document Type:Article
Communicated by:keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:%G eng
Identifiers:ISSN:1528-0012 (Electronic) 0016-5085 (Linking) %R 10.1... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/22245845 [ID No:2]
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