Stem Cells - Induced

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Introduction

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 pluripotent stem cell | Yamanaka Factors | Somatic Cell Nuclear Transfer | Ethics | Organoids | Adult Human Cell Types | Category:Stem Cell

Some Recent Findings

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"

  • Yamanaka Factors Are a set of 4 transcription factors when introduced into cells induces stem cell formation.
  • 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.


  • 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."

Induced Pluripotent Stem Cell

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.

OCT4

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

SOX2

  • Sry-related HMG-Box gene 2
Links: 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 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.[5]
  • Tbx3 transcription factor significantly improves the quality of iPS cells.[6]


Links: Generating iPS Cells from MEFS through Forced Expression of Sox-2, Oct-4, c-Myc, and Klf4


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

OCT4

Links: OMIM - OCT4

SOX2

Links: OMIM - SOX2

NANOG

Links: OMIM - NANOG

LIN28

Links:

Target Genes

Oct4, Nanog, and Sox2 target genes

References

  1. ↑ <pubmed>19672241</pubmed>
  2. ↑ <pubmed>21789202</pubmed>| PLoS One.
  3. ↑ <pubmed>16904174</pubmed>
  4. ↑ <pubmed>18035408</pubmed>
  5. ↑ <pubmed>18594515</pubmed>
  6. ↑ <pubmed>20139965</pubmed>

Reviews

<pubmed>17157222</pubmed> <pubmed>17123233</pubmed> <pubmed>17076989</pubmed>


Articles

<pubmed>19898493</pubmed> <pubmed>17282993</pubmed> <pubmed>17234930</pubmed>

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 |

Additional Images

  • Human induced pluripotent stem cells

    Human induced pluripotent stem cells

  • Reprogramming MEF into ES-like cells

    Reprogramming MEF into ES-like cells

  • Reprogramming MEF into ES-like cells

    Reprogramming MEF into ES-like cells

External Links

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Cite this page: Hill, M.A. (2024, April 18) Embryology Stem Cells - Induced. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Stem_Cells_-_Induced

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