Embryology History - Shinya Yamanaka

From Embryology

Introduction

Shinya Yamanaka

Professor Yamanaka has had a key role to play in identifying the specific 4 factors required alone to transform a cell from adult tissues into a stem cell. These 4 factors have also been called "Yamanaka Factors" and the stem cells formed, by their introduction or expression, are called "induced Pluriopotential Stem Cells" (iPS). This finding[1] has been the basis of many recent stem cell papers. These "Yamanaka Factors" are transcription factors, that also have other developmental roles, and can regulate the expression of a range of other nuclear genes.

Yamanaka Factors:

  • Oct3/4 - Octamer-binding transcription factor 3/4
  • Sox2 - Sry-related HMG-box gene 2
  • Klf4 - Kruppel-like factor 4
  • c-Myc - MYC protooncogene


Links: Induced Stem Cells | Stem Cells | John Gurdon | Sox


Stem Cell Links: Introduction | Timeline | Placental Cord Blood | Adult | Induced | Yamanaka Factors | Somatic Cell Nuclear Transfer | Ethics | Category:Stem Cell

Some Recent Findings

Mouse- embryonic stem cell signaling regulation

The Nobel Prize in Physiology or Medicine 2012 was awarded jointly to Sir John B. Gurdon and Shinya Yamanaka

"for the discovery that mature cells can be reprogrammed to become pluripotent"
  • Generation of Naive-like Porcine Induced Pluripotent Stem Cells Capable of Contributing to Embryonic and Fetal Development[2] "In pluripotent stem cells (PSCs), there are two types: naive and primed. Only the naive type has the capacity for producing chimeric offspring. Mouse PSCs are naive, but human PSCs are in the primed state. Previously reported porcine PSCs appear in the primed state. In this study, putative naive porcine induced pluripotent stem cells (iPSCs) were generated. ...This is the first demonstration of macroscopic, fluorescent chimeras derived from naive-like porcine PSCs, although adult chimeras remain to be produced.:
  • Donor-dependent variations in hepatic differentiation from human-induced pluripotent stem cells[3] "Hepatocytes generated from human induced pluripotent stem cells (hiPSCs) are unprecedented resources for pharmaceuticals and cell therapy. ... In the current study, we developed an improved hepatic differentiation protocol and compared 28 hiPSC lines originated from various somatic cells and derived using retroviruses, Sendai viruses, or episomal plasmids. This comparison indicated that the origins, but not the derivation methods, may be a major determinant of variation in hepatic differentiation."


Recent References | References

Research History

Human iPS cells[4]
  • 1987 - M.D. at Kobe University, worked as a resident in orthopedic surgery at National Osaka Hospital for two years.
  • 1993 - Ph.D. in medicine at Osaka City University and moved to the United States as a postdoctoral fellow at the Gladstone Institute of Cardiovascular Disease, in San Francisco, CA.
  • 1996 - Assistant professor at Osaka City University School of Medicine.
  • 1999 - Associate professor at the Nara Institute of Science and Technology.
  • 2004 - Professor at Kyoto University.
  • 2010 - Director of Center for iPS Cell Research and Application at Kyoto University. Kyoto Prize in Advanced Technology | Lecture text PDF
  • 2012 - The Nobel Prize in Physiology or Medicine 2012 awarded jointly with Sir John B. Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent".

2016 Interview

Development - 2016 Interview with Shinya Yamanaka (inducible Stem Cells)

YouTube Links  
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Links: One Minute Embryology | 2016 Yamanaka inducible stem cells | Embryology Channel

Key Paper

Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors

Cell. 2006 Aug 25;126(4):663-76. Epub 2006 Aug 10.[1]

Takahashi K, Yamanaka S.

Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.

Abstract

Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions. Unexpectedly, Nanog was dispensable. These cells, which we designated iPS (induced pluripotent stem) cells, exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice resulted in tumors containing a variety of tissues from all three germ layers. Following injection into blastocysts, iPS cells contributed to mouse embryonic development. These data demonstrate that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors.

Comment in:

  • A transcriptional logic for nuclear reprogramming.[5]
  • Achieving pluripotency.[6]

Yamanaka Factors

Early mouse Sox2 expression.[7]

Yamanaka Factors[8][9] Are a set of 4 transcription factors when introduced into cells induces stem cell formation. These four transcription factors can be expressed from doxycycline (dox)-inducible lentiviral vectors.

OCT4

  • Transcription factors containing the POU homeodomain
Links: OMIM - OCT4

SOX2

  • Sry-related HMG-Box gene 2


Links: Sox | OMIM - SOX2

KLF4

  • Kruppel-like factor 4, zinc finger protein, transcription factor which acts as both an activator and repressor.
Links: OMIM - KLF4

cMyc

  • The MYC protooncogene encodes a DNA-binding factor that can activate and repress transcription.
  • Ectopic expression of c-Myc can also cause tumorigenicity in offspring.
Links: OMIM - MYC


  • More recently shown that Oct4 together with either Klf4 or c-Myc is sufficient to generate iPS cells from neural stem cells.[10]
  • Tbx3 transcription factor significantly improves the quality of iPS cells.[11]

Historic Embryologists

Embryologists: William Hunter | Wilhelm Roux | Wilhelm His | Julius Kollmann | Hans Spemann | Charles Minot | Ambrosius Hubrecht | Charles Bardeen | Franz Keibel | Franklin Mall | Florence Sabin | George Streeter | George Corner | James Hill | Jan Florian | Thomas Bryce | Thomas Morgan | Ernest Frazer | Francisco Orts-Llorca | José Doménech Mateu | Frederic Lewis | Arthur Meyer | Erich Blechschmidt | Klaus Hinrichsen | Hideo Nishimura | Arthur Hertig | John Rock | Mary Lyon | Nicole Le Douarin | Robert Winston | Fabiola Müller | Ronan O'Rahilly | Robert Edwards | John Gurdon | Shinya Yamanaka | Embryology History | Category:People
Related Historic Researchers  
Santiago Ramón y Cajal | Camillo Golgi

References

  1. 1.0 1.1 Kazutoshi Takahashi, Shinya Yamanaka Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell: 2006, 126(4);663-76 PubMed 16904174
  2. Shuh-hei Fujishiro, Kazuaki Nakano, Yoshihisa Mizukami, Takuya Azami, Yoshikazu Arai, Hitomi Matsunari, Rikiya Ishino, Takashi Nishimura, Masahito Watanabe, Tomoyuki Abe, Yutaka Furukawa, Kazuhiro Umeyama, Shinya Yamanaka, Masatsugu Ema, Hiroshi Nagashima, Yutaka Hanazono Generation of naive-like porcine-induced pluripotent stem cells capable of contributing to embryonic and fetal development. Stem Cells Dev.: 2013, 22(3);473-82 PubMed 22889279
  3. Masatoshi Kajiwara, Takashi Aoi, Keisuke Okita, Ryosuke Takahashi, Haruhisa Inoue, Naoya Takayama, Hiroshi Endo, Koji Eto, Junya Toguchida, Shinji Uemoto, Shinya Yamanaka Donor-dependent variations in hepatic differentiation from human-induced pluripotent stem cells. Proc. Natl. Acad. Sci. U.S.A.: 2012, 109(31);12538-43 PubMed 22802639
  4. Kazutoshi Takahashi, Megumi Narita, Midori Yokura, Tomoko Ichisaka, Shinya Yamanaka Human induced pluripotent stem cells on autologous feeders. PLoS ONE: 2009, 4(12);e8067 PubMed 19956543 | PMC2780725 | PLoS One
  5. Kit T Rodolfa, Kevin Eggan A transcriptional logic for nuclear reprogramming. Cell: 2006, 126(4);652-5 PubMed 16923385
  6. Kim Baumann Achieving pluripotency. Nat. Rev. Mol. Cell Biol.: 2010, 11(10);677 PubMed 20861870
  7. Maria Keramari, Janet Razavi, Karen A Ingman, Christoph Patsch, Frank Edenhofer, Christopher M Ward, Susan J Kimber Sox2 is essential for formation of trophectoderm in the preimplantation embryo. PLoS ONE: 2010, 5(11);e13952 PubMed 21103067 | PMC2980489 | PLoS One.
  8. Kazutoshi Takahashi, Shinya Yamanaka Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell: 2006, 126(4);663-76 PubMed 16904174
  9. Kazutoshi Takahashi, Koji Tanabe, Mari Ohnuki, Megumi Narita, Tomoko Ichisaka, Kiichiro Tomoda, Shinya Yamanaka Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell: 2007, 131(5);861-72 PubMed 18035408
  10. Jeong Beom Kim, Holm Zaehres, Guangming Wu, Luca Gentile, Kinarm Ko, Vittorio Sebastiano, Marcos J Araúzo-Bravo, David Ruau, Dong Wook Han, Martin Zenke, Hans R Schöler Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature: 2008, 454(7204);646-50 PubMed 18594515
  11. Jianyong Han, Ping Yuan, Henry Yang, Jinqiu Zhang, Boon Seng Soh, Pin Li, Siew Lan Lim, Suying Cao, Junliang Tay, Yuriy L Orlov, Thomas Lufkin, Huck-Hui Ng, Wai-Leong Tam, Bing Lim Tbx3 improves the germ-line competency of induced pluripotent stem cells. Nature: 2010, 463(7284);1096-100 PubMed 20139965

Reviews


Articles

Shinya Yamanaka, Helen M Blau Nuclear reprogramming to a pluripotent state by three approaches. Nature: 2010, 465(7299);704-12 PubMed 20535199

Kazutoshi Takahashi, Koji Tanabe, Mari Ohnuki, Megumi Narita, Tomoko Ichisaka, Kiichiro Tomoda, Shinya Yamanaka Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell: 2007, 131(5);861-72 PubMed 18035408

Kazutoshi Takahashi, Shinya Yamanaka Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell: 2006, 126(4);663-76 PubMed 16904174


Journal of Visualized Experiments - Generating iPS Cells from MEFS through Forced Expression of Sox-2, Oct-4, c-Myc, and Klf4

Search PubMed

Search PubMed Now: Yamanaka+S | induced pluripotent stem cell |

Terms

  • ESC - acronym for Embryonic Stem Cell. Stem cells that have been derived from an embryonic source, usually the blastocyst.
  • hiPSC - acronym for human induced pluripotent stem cell. Stem cells originating from human somatic tissues that have been induced to differentiate into a stem cell by Yamanaka factors.
  • iPS cell - (iPSC) acronym for induced Pluripotent Stem cell. Stem cells originating from somatic tissues of animals or humans that have been induced to differentiate into a stem cell by Yamanaka factors.


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Cite this page: Hill, M.A. 2017 Embryology Embryology History - Shinya Yamanaka. Retrieved December 18, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Embryology_History_-_Shinya_Yamanaka

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