Stem Cells - Induced

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Mouse- embryonic stem cell signaling regulation

The term "induced stem cell" refers to the new methods of gene introduction and expression that generate stem cells from both embryo and adult tissues.

A useful guide (online PDF document) to stem cells was produced in a report by the National Institute of Health (NIH, USA, May 2000) Stem Cells: A Primer (note large size - 4.84 Mb) and more recently NIH has established a Stem Cell information page.

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

Some Recent Findings

STAP now discredited.
  • Is Stimulus-triggered fate conversion of somatic cells into pluripotency (STAP) Real? RIKEN Panel Finds Misconduct in Reprogrammed Stem Cell Papers press release April 1, 2014 | Science April 2014 | Japanese research institute has opened an investigation into this groundbreaking stem cell study after concerns were raised about its credibility. The RIKEN investigation follows allegations on blog sites about the use of duplicated images in Obokata’s papers, and numerous failed attempts to replicate her results. Nature
  • 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"
  • Shinya Yamanaka Yamanaka Factors are a set of 4 transcription factors when introduced into cells induces stem cell formation. Search PubMed
  • John Gurdon used nuclear transplantation and cloning to show that the nucleus of a differentiated somatic cell retains the totipotency necessary to form a whole organism. 2003 Current Biology Interview PMID 14521852 2009 Interview - "The birth of cloning" PMID 19132124 Search PubMed
  • The tumorigenicity of human embryonic and induced pluripotent stem cells PMID: 21390058 "Until recently, it was assumed that human induced pluripotent stem cells (HiPSCs) would behave like their embryonic counterparts in respect to their tumorigenicity. However, a rapidly accumulating body of evidence suggests that there are important genetic and epigenetic differences between these two cell types, which seem to influence their tumorigenicity."
  • iPS cells produce viable mice through tetraploid complementation[1] "Here we report the generation of several iPS cell lines that are capable of generating viable, live-born progeny by tetraploid complementation. These iPS cells maintain a pluripotent potential that is very close to ES cells generated from in vivo or nuclear transfer embryos. We demonstrate the practicality of using iPS cells as useful tools for the characterization of cellular reprogramming and developmental potency, and confirm that iPS cells can attain true pluripotency that is similar to that of ES cells."
More recent papers
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches

Search term: Induced Stem Cells

Lajmi Lakhal-Chaieb, Celia M T Greenwood, Mohamed Ouhourane, Kaiqiong Zhao, Belkacem Abdous, Karim Oualkacha A smoothed EM-algorithm for DNA methylation profiles from sequencing-based methods in cell lines or for a single cell type. Stat Appl Genet Mol Biol: 2017; PubMed 29055941

Ming-Ching Ho, Ching-Ying Huang, Jia-Jung Lee, Shih-Han Hsu, Yu-Che Cheng, Yu-Hung Hsu, Daw-Yang Hwang, Huai-En Lu, Hung-Chun Chen, Patrick C H Hsieh Generation of an induced pluripotent stem cell line, IBMS-iPSC-014-05, from a female autosomal dominant polycystic kidney disease patient carrying a common mutation of R803X in PKD2. Stem Cell Res: 2017, 25;38-41 PubMed 29055226

Alexander Williams, Sana Nasim, Manuel Salinas, Arash Moshkforoush, Nikolaos Tsoukias, Sharan Ramaswamy A "sweet-spot" for fluid-induced oscillations in the conditioning of stem cell-based engineered heart valve tissues. J Biomech: 2017; PubMed 29054608

Saba Haq, Bharathi Suresh, Suresh Ramakrishna Deubiquitylating enzymes as cancer stem cell therapeutics. Biochim. Biophys. Acta: 2017; PubMed 29054474

Curtis R Warren, Chad A Cowan Humanity in a Dish: Population Genetics with iPSCs. Trends Cell Biol.: 2017; PubMed 29054332

Induced Pluripotent Stem Cell

2016 Interview with Shinya Yamanaka

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

YouTube Links  
Note - this may include both internal and external movie links.

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

Prof. Shinya Yamanaka ia a Nobel laureate and the developer of induced stem cells.

Rat induced pluripotential stem cell protocol[2]

(iPS cell) A reprogrammed adult stem cell to form an embryonic stem cell, from which tissues or whole animals can develop. Can be generated by the expression of just four specific transcription factors.

Links: Nature Jul09 | ABC - Mice pups bred from adult stem cells

Yamanaka Factors

Reprogramming MEF into ES-like cells 03.jpg

Yamanaka Factors[3][4] 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.


  • Octamer-binding transcription factor 3/4
  • Transcription factors containing the POU homeodomain

Links: OMIM - OCT4


Early mouse Sox2 expression.[5]
  • Sry-related HMG-Box gene 2.
  • Sox2 is first expressed in very early (morula, blastocyst) development.
  • Forms a trimeric transcription complex with OCT4.
  • Gene targets - YES1, FGF4, UTF1 and ZFP206.

Links: | Sox | OMIM - SOX2


  • Kruppel-like factor 4, zinc finger protein, transcription factor which acts as both an activator and repressor.
  • alternative names: Epithelial zinc finger protein EZF or Gut-enriched krueppel-like factor

Links: OMIM - KLF4


  • 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.
More recently shown that Oct4 together with either Klf4 or c-Myc is sufficient to generate iPS cells from neural stem cells.[6]
  • Tbx3 transcription factor significantly improves the quality of iPS cells.[7]

Links: OMIM - MYC

Generation of human melanocytes from induced pluripotent stem cells

PLoS One. 2011 Jan 13;6(1):e16182.

Ohta S, Imaizumi Y, Okada Y, Akamatsu W, Kuwahara R, Ohyama M, Amagai M, Matsuzaki Y, Yamanaka S, Okano H, Kawakami Y. Source Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan. Abstract Epidermal melanocytes play an important role in protecting the skin from UV rays, and their functional impairment results in pigment disorders. Additionally, melanomas are considered to arise from mutations that accumulate in melanocyte stem cells. The mechanisms underlying melanocyte differentiation and the defining characteristics of melanocyte stem cells in humans are, however, largely unknown. In the present study, we set out to generate melanocytes from human iPS cells in vitro, leading to a preliminary investigation of the mechanisms of human melanocyte differentiation. We generated iPS cell lines from human dermal fibroblasts using the Yamanaka factors (SOX2, OCT3/4, and KLF4, with or without c-MYC). These iPS cell lines were subsequently used to form embryoid bodies (EBs) and then differentiated into melanocytes via culture supplementation with Wnt3a, SCF, and ET-3. Seven weeks after inducing differentiation, pigmented cells expressing melanocyte markers such as MITF, tyrosinase, SILV, and TYRP1, were detected. Melanosomes were identified in these pigmented cells by electron microscopy, and global gene expression profiling of the pigmented cells showed a high similarity to that of human primary foreskin-derived melanocytes, suggesting the successful generation of melanocytes from iPS cells. This in vitro differentiation system should prove useful for understanding human melanocyte biology and revealing the mechanism of various pigment cell disorders, including melanoma.

PMID 21249204

Thomson Factors


Links: OMIM - OCT4


Links: OMIM - SOX2


Links: Nanog | OMIM - NANOG



Target Genes

Oct4, Nanog, and Sox2 target genes


  1. Xiao-yang Zhao, Wei Li, Zhuo Lv, Lei Liu, Man Tong, Tang Hai, Jie Hao, Chang-long Guo, Qing-wen Ma, Liu Wang, Fanyi Zeng, Qi Zhou iPS cells produce viable mice through tetraploid complementation. Nature: 2009, 461(7260);86-90 PubMed 19672241
  2. Sanae Hamanaka, Tomoyuki Yamaguchi, Toshihiro Kobayashi, Megumi Kato-Itoh, Satoshi Yamazaki, Hideyuki Sato, Ayumi Umino, Yukiko Wakiyama, Mami Arai, Makoto Sanbo, Masumi Hirabayashi, Hiromitsu Nakauchi Generation of germline-competent rat induced pluripotent stem cells. PLoS ONE: 2011, 6(7);e22008 PubMed 21789202 | PLoS One.
  3. 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
  4. 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
  5. 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.
  6. 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
  7. 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


Jose M Moraleda, Miguel Blanquer, Patricia Bleda, Paqui Iniesta, Francisco Ruiz, Sonia Bonilla, Carmen Cabanes, Lucía Tabares, Salvador Martinez Adult stem cell therapy: dream or reality? Transpl. Immunol.: 2006, 17(1);74-7 PubMed 17157222

Marta Serafini, Catherine M Verfaillie Pluripotency in adult stem cells: state of the art. Semin. Reprod. Med.: 2006, 24(5);379-88 PubMed 17123233

Augusto Pessina, Laura Gribaldo The key role of adult stem cells: therapeutic perspectives. Curr Med Res Opin: 2006, 22(11);2287-300 PubMed 17076989


Jacob Hanna, Krishanu Saha, Bernardo Pando, Jeroen van Zon, Christopher J Lengner, Menno P Creyghton, Alexander van Oudenaarden, Rudolf Jaenisch Direct cell reprogramming is a stochastic process amenable to acceleration. Nature: 2009, 462(7273);595-601 PubMed 19898493

Jeffrey J Ross, Catherine M Verfaillie Evaluation of neural plasticity in adult stem cells. Philos. Trans. R. Soc. Lond., B, Biol. Sci.: 2008, 363(1489);199-205 PubMed 17282993

David A Prentice, Gene Tarne Treating diseases with adult stem cells. Science: 2007, 315(5810);328 PubMed 17234930

Search PubMed

Search PubMed: Feb 2007 "adult stem cells" 811 reference articles of which 367 were reviews.

Search PubMed Now: adult stem cells | induced pluripotent stem cell |

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Cite this page: Hill, M.A. 2017 Embryology Stem Cells - Induced. Retrieved October 24, 2017, from

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