The Epigenetics of Adult (Somatic) Stem Cells

Eilertsen, Kenneth J.; Floyd, Z. Elizabeth; Gimble, Jeffrey M.

doi:10.1615/critreveukargeneexpr.v18.i3.10

Cited by 21 publications

(9 citation statements)

References 147 publications

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“…These observations suggest that ASCs may be more responsive to adipogenic stimuli due to their tissue of origin. While it is possible that epigenetic programming mechanism during tissue development could account for these findings, further studies will be required to explore this possibility (Eilertsen et al, 2008). …”

Section: Discussionmentioning

confidence: 99%

Stromal stem cells from adipose tissue and bone marrow of age‐matched female donors display distinct immunophenotypic profiles

Pachón-Peña

Tucker

et al. 2010

Journal Cellular Physiology

173

146

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Adipose tissue is composed of lipid-filled mature adipocytes and a heterogeneous stromal vascular fraction (SVF) population of cells. Similarly, the bone marrow (BM) is composed of multiple cell types including adipocytes, hematopoietic, osteoprogenitor, and stromal cells necessary to support hematopoiesis. Both adipose and BM contain a population of mesenchymal stromal/stem cells with the potential to differentiate into multiple lineages, including adipogenic, chondrogenic, and osteogenic cells, depending on the culture conditions. In this study we have shown that human adipose-derived stem cells (ASCs) and bone marrow mesenchymal stem cells (BMSCs) populations display a common expression profile for many surface antigens, including CD29, CD49c, CD147, CD166, and HLA-abc. Nevertheless, significant differences were noted in the expression of CD34 and its related protein, PODXL, CD36, CD 49f, CD106, and CD146. Furthermore, ASCs displayed more pronounced adipogenic differentiation capability relative to BMSC based on Oil Red staining (7-fold vs. 2.85-fold induction). In contrast, no difference between the stem cell types was detected for osteogenic differentiation based on Alizarin Red staining. Analysis by RT-PCR demonstrated that both the ASC and BMSC differentiated adipocytes and osteoblast displayed a significant upregulation of lineage-specific mRNAs relative to the undifferentiated cell populations; no significant differences in fold mRNA induction was noted between ASCs and BMSCs. In conclusion, these results demonstrate human ASCs and BMSCs display distinct immunophenotypes based on surface positivity and expression intensity as well as differences in adipogenic differentiation. The findings support the use of both human ASCs and BMSCs for clinical regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Stromal stem cells from adipose tissue and bone marrow of age‐matched female donors display distinct immunophenotypic profiles

Pachón-Peña

Tucker

et al. 2010

Journal Cellular Physiology

173

146

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“…52,54,59 Whether or not the tissue of origin regulates the epigenetic memory of MSCs and their subsequent differentiation potential remains to be determined. 60 …”

Section: Stromal Cellsmentioning

confidence: 99%

Stromal cells and stem cells in clinical bone regeneration

et al. 2015

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Stem-cell-mediated bone repair has been used in clinical trials for the regeneration of large craniomaxillofacial defects, to slow the process of bone degeneration in patients with osteonecrosis of the femoral head and for prophylactic treatment of distal tibial fractures. Successful regenerative outcomes in these investigations have provided a solid foundation for wider use of stromal cells in skeletal repair therapy. However, employing stromal cells to facilitate or enhance bone repair is far from being adopted into clinical practice. Scientific, technical, practical and regulatory obstacles prevent the widespread therapeutic use of stromal cells. Ironically, one of the major challenges lies in the limited understanding of the mechanisms via which transplanted cells mediate regeneration. Animal models have been used to provide insight, but these models largely fail to reproduce the nuances of human diseases and bone defects. Consequently, the development of targeted approaches to optimize cell-mediated outcomes is difficult. In this Review, we highlight the successes and challenges reported in several clinical trials that involved the use of bone-marrow-derived mesenchymal or adipose-tissue-derived stromal cells. We identify several obstacles blocking the mainstream use of stromal cells to enhance skeletal repair and highlight technological innovations or areas in which novel techniques might be particularly fruitful in continuing to advance the field of skeletal regenerative medicine.

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“…Similarly, histone-modifying enzymes involved in epigenetic modification are also able to dynamically remodel the nucleosome [31][32][33]. Histone methylation, such as H3K4me3 and H3K27me3, has been linked to the regulation of developmental genes and the maintenance of pluripotency in embryonic stem cell populations [34,35].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic mechanisms in cardiac development and disease

Vallaster¹,

Vallaster²,

Wu³

2012

ABBS

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During mammalian development, cardiac specification and ultimately lineage commitment to a specific cardiac cell type is accomplished by the action of specific transcription factors (TFs) and their meticulous control on an epigenetic level. In this review, we detail how cardiacspecific TFs function in concert with nucleosome remodeling and histone-modifying enzymes to regulate a diverse network of genes required for processes such as cell growth and proliferation, or epithelial to mesenchymal transition (EMT), for instance. We provide examples of how several cardiac TFs, such as Nkx2.5, WHSC1, Tbx5, and Tbx1, which are associated with developmental and congenital heart defects, are required for the recruitment of histone modifiers, such as Jarid2, p300, and Ash2l, and components of ATP-dependent remodeling enzymes like Brg1, Baf60c, and Baf180. Binding of these TFs to their respective sites at cardiac genes coincides with a distinct pattern of histone marks, indicating that the precise regulation of cardiac gene networks is orchestrated by interactions between TFs and epigenetic modifiers. Furthermore, we speculate that an epigenetic signature, comprised of TF occupancy, histone modifications, and overall chromatin organization, is an underlying mechanism that governs cardiac morphogenesis and disease.

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The Epigenetics of Adult (Somatic) Stem Cells

Cited by 21 publications

References 147 publications

Stromal stem cells from adipose tissue and bone marrow of age‐matched female donors display distinct immunophenotypic profiles

Stromal stem cells from adipose tissue and bone marrow of age‐matched female donors display distinct immunophenotypic profiles

Stromal cells and stem cells in clinical bone regeneration

Epigenetic mechanisms in cardiac development and disease

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