Open Access

Genome-wide analysis of murine bone marrow‑derived very small embryonic-like stem cells reveals that mitogenic growth factor signaling pathways play a crucial role in the quiescence and ageing of these cells

  • Authors:
    • Katarzyna Mierzejewska
    • Jinbeom Heo
    • Jeong Wook Kang
    • Hyunsook Kang
    • Janina Ratajczak
    • Mariusz Z. Ratajczak
    • Magda Kucia
    • Dong-Myung Shin
  • View Affiliations

  • Published online on: May 23, 2013     https://doi.org/10.3892/ijmm.2013.1389
  • Pages: 281-290
  • Copyright: © Mierzejewska et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

It has been postulated that the most primitive population of stem cells, Oct4+Sca-1+Lin-CD45- very small embryonic-like stem cells (VSELs), differentiate into tissue-committed stem cells in adult mice. However, Oct4+ VSELs remain quiescent in adult tissues and do not form teratomas. In thi study, we report the characteristics of the VSEL transcriptome by gene set enrichment analysis employing a microarray database established from 20 murine bone marrow-derived, FACS-sorted VSELs in comparison with hematopoietic stem cells and embryonic stem cells. In the Oct4+ VSELs, we observed the upregulation of tissue-specific gene sets and a gene set encoding the complement-coagulation cascade. By contrast, in the VSELs, we observed the downregulation of genes involved in the UV radiation response, mRNA processing and mitogenic growth factor signaling [e.g., insulin-like growth factor‑1 (IGF-1) and neurotrophic tyrosine kinase receptor A (TRKA), as well as the ERK and PI3K pathways]. Employing leading-edge subset analysis and real-time PCR assays, we observed that several genes, such as growth factor receptor-bound protein 2 (Grb2), son of sevenless homolog 1 (Sos1), SHC (Src homology 2 domain containing) transforming protein 1 (Shc1), mitogen-activated protein kinase kinase 1 (Map2k1), v-akt murine thymoma viral oncogene homolog 3 (Akt3), Elk1, ribosomal protein S6 kinase, 90kDa, polypeptide 3 (Rps6kA3), glycogen synthase kinase 3β (Gsk3β) and casein kinase 2, alpha 1 polypeptide (Csnk2A1), which are involved in mitogenic growth factor signaling pathways, were commonly downregulated in the VSELs. Notably, this repression was reversed in the VSELs co-cultured over a C2C12 supportive cell-line, whereby they are induced to form VSEL-derived spheres (VSEL-DSs); thus, they are enriched, forming more differentiated stem cells. Therefore, we suggest that the repression of mitogenic growth factor signaling (e.g., through the IGF-1 receptor) may prevent uncontrolled Oct4+ VSEL proliferation and teratoma formation. Thus, restoring the responsiveness to mitogenic growth factors may be a crucial step in employing these cells in regenerative medicine.
View Figures
View References

Related Articles

Journal Cover

August 2013
Volume 32 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Mierzejewska K, Heo J, Kang JW, Kang H, Ratajczak J, Ratajczak MZ, Kucia M and Shin D: Genome-wide analysis of murine bone marrow‑derived very small embryonic-like stem cells reveals that mitogenic growth factor signaling pathways play a crucial role in the quiescence and ageing of these cells. Int J Mol Med 32: 281-290, 2013
APA
Mierzejewska, K., Heo, J., Kang, J.W., Kang, H., Ratajczak, J., Ratajczak, M.Z. ... Shin, D. (2013). Genome-wide analysis of murine bone marrow‑derived very small embryonic-like stem cells reveals that mitogenic growth factor signaling pathways play a crucial role in the quiescence and ageing of these cells. International Journal of Molecular Medicine, 32, 281-290. https://doi.org/10.3892/ijmm.2013.1389
MLA
Mierzejewska, K., Heo, J., Kang, J. W., Kang, H., Ratajczak, J., Ratajczak, M. Z., Kucia, M., Shin, D."Genome-wide analysis of murine bone marrow‑derived very small embryonic-like stem cells reveals that mitogenic growth factor signaling pathways play a crucial role in the quiescence and ageing of these cells". International Journal of Molecular Medicine 32.2 (2013): 281-290.
Chicago
Mierzejewska, K., Heo, J., Kang, J. W., Kang, H., Ratajczak, J., Ratajczak, M. Z., Kucia, M., Shin, D."Genome-wide analysis of murine bone marrow‑derived very small embryonic-like stem cells reveals that mitogenic growth factor signaling pathways play a crucial role in the quiescence and ageing of these cells". International Journal of Molecular Medicine 32, no. 2 (2013): 281-290. https://doi.org/10.3892/ijmm.2013.1389