Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Mar;15(3):244-53.
doi: 10.1002/embr.201338254. Epub 2014 Feb 14.

Dedifferentiation and reprogramming: origins of cancer stem cells

Dinorah Friedmann-Morvinski  1 , Inder M Verma
Affiliations
Review

Dedifferentiation and reprogramming: origins of cancer stem cells

Dinorah Friedmann-Morvinski et al. EMBO Rep. 2014 Mar.

Abstract

Regenerative medicine aims to replace the lost or damaged cells in the human body through a new source of healthy transplanted cells or by endogenous repair. Although human embryonic stem cells were first thought to be the ideal source for cell therapy and tissue repair in humans, the discovery by Yamanaka and colleagues revolutionized the field. Almost any differentiated cell can be sent back in time to a pluripotency state by expressing the appropriate transcription factors. The process of somatic reprogramming using Yamanaka factors, many of which are oncogenes, offers a glimpse into how cancer stem cells may originate. In this review we discuss the similarities between tumor dedifferentiation and somatic cell reprogramming and how this may pose a risk to the application of this new technology in regenerative medicine.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Glioblastoma tumors induced by oncogenic lentivirus either in neurons or in glia in the cortex initially express differentiation markers (e.g., Tuj1 and GFAP, respectively), but as tumor progresses, these markers decrease and stem/progenitor markers become predominantly expressed (like nestin and Sox2) [20].
Figure 2
Figure 2
An astrocyte transduced with LV-Hras-shp53 dedifferentiates/reprograms to a progenitor/stem cell state, leading to tumorsphere formation. These tumorspheres when transplanted orthotopically in the brain of mice lead to glioma tumors. The same astrocytes transduced with a lentivector carrying the four transcription factors (Oct-4, Klf-4, Sox2, and myc) reprogram and form iPS colonies than when transplanted s.c. into mice develop teratomas.
Figure 3
Figure 3
Normal mechanism of neuronal differentiation: Neural stem cell can self-renew, go through an intermediate progenitor cell, and differentiate into oligodendrocytes, astrocytes, neurons, and endothelial cells. In the formation of glioblastoma, the transformed neurons, astrocytes, and possibly oligodendrocytes can dedifferentiate/reprogram to become cancer stem cells (CSCs), which can then continue to self-proliferate and differentiate to more transformed neurons and astrocytes. The transformed neurons and astrocytes can also transdifferentiate into endothelial cells (TDECs), which can again dedifferentiate to CSCs.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kaiser LR. The future of multihospital systems. Top Health Care Financ. 1992;18:32–45. - PubMed
    1. Lysaght MJ, Crager J. Origins. Tissue Eng Part A. 2009;15:1449–1450. - PubMed
    1. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–676. - PubMed
    1. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318:1917–1920. - PubMed
    1. Briggs R, King TJ. Transplantation of living nuclei from blastula cells into enucleated frogs' eggs. Proc Natl Acad Sci USA. 1952;38:455–463. - PMC - PubMed

Publication types

MeSH terms