Stem Cell Reviews and Reports

, Volume 6, Issue 2, pp 307–316 | Cite as

Epiblast/Germ Line Hypothesis of Cancer Development Revisited: Lesson from the Presence of Oct-4+ Cells in Adult Tissues

  • Mariusz Z. RatajczakEmail author
  • Dong-Myung Shin
  • Rui Liu
  • Wojtek Marlicz
  • Maciej Tarnowski
  • Janina Ratajczak
  • Magda KuciaEmail author


The morphology of several tumors mimics developmentally early tissues; tumors often express early developmental markers characteristic for the germ line lineage. Recently, our group identified a population of very small stem cells (SCs) in murine bone marrow (BM) and other adult organs that express several markers characteristic for epiblast/germ line-derived SCs. We named these rare cells “Very Small Embryonic/Epiblast-like Stem Cells (VSELs).” We hypothesized that these cells that express both epiblast and germ line markers are deposited during early gastrulation in developing tissues and organs and play an important role in the turnover of tissue-committed (TC) SCs. To support this, we envision that the germ line is not only the origin of SCs, but also remains as a scaffold or back-up for the SC compartment in adult life. Furthermore, we noticed that VSELs are protected from uncontrolled proliferation and teratoma formation by a unique DNA methylation pattern in some developmentally crucial imprinted genes, which show hypomethylation or erasure of imprints in paternally methylated genes and hypermethylation of imprints in the maternally methylated. In pathological situations, however, we hypothesize that VSELs could be involved in the development of several malignancies. Therefore, potential involvement of VSELs in cancerogenesis could support century-old concepts of embryonic rest- or germ line-origin hypotheses of cancer development. However, we are aware that this working hypothesis requires further direct experimental confirmation.


VSELs Oct-4 Cancer testis antigens Germ line 



Bone marrow


Bone marrow mononuclear cell


Cancer testis


Differently methylated region


Days post-conception


Embryonic germ cell


Embryonic stem cell


Fluorescence-activated cell sorting


Flow cytometry


Germ cell


Hematopoietic stem cell


Inner cell mass


Insulin-like growth factor 1 receptor


Insulin-like growth factor 2


Igf2 receptor


ImageStream system


Primordial germ cell


Pluripotent stem cell


Ras protein-specific guanine nucleotide-releasing factor 1


Stem cell


Stage-specific embryonic antigen-1


Tissue-committed stem cell


Very small embryonic/epiblast-like stem cell



This work is supported by NIH grants R01 CA106281-01 and R01 DK074720 and the Stella and Henry Hoenig Endowment to MZR NIH grant P20RR018733 from the National Center for Research Resources to MK and European Union structural funds, Innovative Economy Operational Program POIG. 01.01.02-00-109/09-00.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Mariusz Z. Ratajczak
    • 1
    Email author
  • Dong-Myung Shin
    • 1
  • Rui Liu
    • 1
  • Wojtek Marlicz
    • 2
  • Maciej Tarnowski
    • 1
  • Janina Ratajczak
    • 1
  • Magda Kucia
    • 1
    Email author
  1. 1.Stem Cell Institute at the James Graham Brown Cancer CenterUniversity of LouisvilleLouisvilleUSA
  2. 2.Department of PathophysiologyPomeranian Medical UniversitySzczecinPoland

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