Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency.

Cell
Jacob HannaRudolf Jaenisch

Abstract

Pluripotent cells can be derived from fibroblasts by ectopic expression of defined transcription factors. A fundamental unresolved question is whether terminally differentiated cells can be reprogrammed to pluripotency. We utilized transgenic and inducible expression of four transcription factors (Oct4, Sox2, Klf4, and c-Myc) to reprogram mouse B lymphocytes. These factors were sufficient to convert nonterminally differentiated B cells to a pluripotent state. However, reprogramming of mature B cells required additional interruption with the transcriptional state maintaining B cell identity by either ectopic expression of the myeloid transcription factor CCAAT/enhancer-binding-protein-alpha (C/EBPalpha) or specific knockdown of the B cell transcription factor Pax5. Multiple iPS lines were clonally derived from both nonfully and fully differentiated B lymphocytes, which gave rise to adult chimeras with germline contribution, and to late-term embryos when injected into tetraploid blastocysts. Our study provides definite proof for the direct nuclear reprogramming of terminally differentiated adult cells to pluripotency.

References

Oct 1, 1992·Research in Immunology·C J PaigeG E Wu
Apr 1, 1991·European Journal of Immunology·P SanchezP A Cazenave
Mar 10, 2001·Molecular Reproduction and Development·T Wakayama, R Yanagimachi
May 2, 2001·Proceedings of the National Academy of Sciences of the United States of America·K EgganR Jaenisch
Mar 5, 2002·Nature·Konrad Hochedlinger, Rudolf Jaenisch
May 15, 2002·The Biochemical Journal·Dipak P Ramji, Pelagia Foka
Jul 6, 2002·Science·Ingvild MikkolaMeinrad Busslinger
Apr 30, 2003·The Journal of Experimental Medicine·Philipp OberdoerfferKlaus Rajewsky
Aug 7, 2003·Proceedings of the National Academy of Sciences of the United States of America·Xin WangMarkus Grompe
Mar 3, 2004·Nature·Kevin EgganRudolf Jaenisch
May 28, 2004·Cell·Huafeng XieThomas Graf
Sep 7, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Vance B MatthewsGeorge C T Yeoh
Sep 16, 2004·European Journal of Immunology·Craig D MilneChristopher J Paige
Jun 21, 2005·Current Biology : CB·Kimiko InoueAtsuo Ogura
Sep 13, 2005·Cell·Laurie A BoyerRichard A Young
Mar 23, 2006·Annual Review of Immunology·David JungFrederick W Alt
May 18, 2006·Annual Review of Cell and Developmental Biology·J B Gurdon
Feb 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jinsong LiPeter Mombaerts
Apr 19, 2007·Nature Immunology·César CobaledaMeinrad Busslinger
Jun 20, 2007·Annual Review of Genetics·Grace Teng, F Nina Papavasiliou
Jun 23, 2007·Stem Cells·C Bart RountreeGay M Crooks
Aug 29, 2007·Nature Biotechnology·Alexander MeissnerRudolf Jaenisch
Nov 22, 2007·Science·Junying YuJames A Thomson
Dec 7, 2007·Nature Biotechnology·Masato NakagawaShinya Yamanaka
Mar 29, 2008·Cell Stem Cell·Marius WernigRudolf Jaenisch
Mar 29, 2008·Cell Stem Cell·Matthias StadtfeldKonrad Hochedlinger
Apr 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Marius WernigRudolf Jaenisch
Jul 5, 2008·Nature Protocols·In-Hyun ParkGeorge Q Daley
Oct 11, 2008·Science·Keisuke OkitaShinya Yamanaka

❮ Previous
Next ❯

Citations

Apr 25, 2012·Cellular and Molecular Life Sciences : CMLS·Masaaki KitadaMari Dezawa
Jan 1, 2013·Cellular and Molecular Life Sciences : CMLS·Kei Miyamoto, J B Gurdon
Feb 16, 2010·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Shabnam ShalapourThomas Kammertoens
May 6, 2009·Pediatric Cardiology·Jason T LamKarl-Ludwig Laugwitz
Feb 17, 2009·Biogerontology·Jan O Nehlin, Torben Barington
Mar 9, 2011·Journal of Assisted Reproduction and Genetics·Mei I LaiSyahril Abdullah
Jul 30, 2008·Transgenic Research·Alexander Kind, Angelika Schnieke
Jul 4, 2012·Current Diabetes Reports·Insa S Schroeder
Feb 17, 2010·International Journal of Hematology·Shinji Masui
May 18, 2012·International Journal of Hematology·Hiroshi WataraiHaruhiko Koseki
Jun 29, 2013·International Journal of Hematology·Keiki KumanoMineo Kurokawa
Jan 6, 2011·Journal of Cardiovascular Translational Research·Almudena Martinez-FernandezAndre Terzic
May 29, 2012·Journal of Cardiovascular Translational Research·Elena Matsa, Chris Denning
Jan 7, 2011·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Dov Zipori
May 9, 2013·Ageing Research Reviews·Shauna H Yuan, Mason Shaner
Aug 17, 2010·Expert Reviews in Molecular Medicine·S Tamir Rashid, Ludovic Vallier
Feb 16, 2011·Cell Research·Bernadett Papp, Kathrin Plath
Sep 13, 2013·Gene Therapy·A Wagnerova, R Gardlik
Jun 15, 2011·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Haipeng ShaoElaine S Jaffe
Jan 21, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Janka MátraiThierry VandenDriessche
Apr 2, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Lars U W MüllerDavid A Williams
May 19, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Bonan ZhongHans-Peter Kiem
May 30, 2008·Nature·Tarjei S MikkelsenAlexander Meissner
Jan 29, 2010·Nature·Thomas VierbuchenMarius Wernig
Jul 21, 2010·Nature·K KimG Q Daley
Jan 20, 2012·Nature·Daisy A Robinton, George Q Daley
Oct 2, 2012·Nature·Marganit FaragoYehudit Bergman
Oct 25, 2013·Nature·Effie Apostolou, Konrad Hochedlinger
Jan 20, 2009·Nature Biotechnology·Styliani MarkoulakiRudolf Jaenisch
Jul 11, 2009·Nature Biotechnology·Kyoko MiuraShinya Yamanaka
Oct 15, 2011·Nature Biotechnology·Thomas Vierbuchen, Marius Wernig
Dec 23, 2008·Nature Cell Biology·Vilma BarrocaPierre Fouchet
Aug 28, 2009·Nature Genetics·Thomas Graf
Dec 17, 2009·Nature Methods·Bryce W CareyRudolf Jaenisch
Dec 30, 2009·Nature Methods·Thomas P Zwaka
Mar 19, 2011·Nature Reviews. Genetics·Kathrin Plath, William E Lowry
May 18, 2013·Nature Reviews. Genetics·Yosef BuganimRudolf Jaenisch

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Cell Fate Specification

Cell fate specification is determined by complex signal transduction pathways including Notch and the Sonic hedgehog signaling pathway. Here is the latest research on regulation of cell fate determination.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

B cells: Gene Expression

B lymphocytes are white blood cells that play a role in the adaptive immune system by secreting antibodies. Here is the latest research on gene expression in B cells.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Cell eTOC

Cell is a scientific journal publishing research across a broad range of disciplines within the life sciences field. Discover the latest research from Cell here.