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Sca-1+ cells from fetal heart with high aldehyde dehydrogenase activity exhibit enhanced gene expression for self-renewal, proliferation, and survival.

Dey D, Pan G, Varma NR, Palaniyandi SS - Oxid Med Cell Longev (2015)

Bottom Line: The ALDH(high) fraction also exhibited significant increase in proliferation and pro-survival gene expression.ALDH(high) cells showed increased resistance against aldehyde challenge compared to ALDH(low) cells.These results indicate that ALDH(high) subpopulation of the cultured human fetal cells has enhanced self-renewal, multipotency, high proliferation, and survival, indicating that this might represent a primitive stem cell population within the fetal human heart.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA ; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

ABSTRACT
Stem/progenitor cells from multiple tissues have been isolated based on enhanced activity of cytosolic aldehyde dehydrogenase (ALDH) enzyme. ALDH activity has emerged as a reliable marker for stem/progenitor cells, such that ALDH(bright/high) cells from multiple tissues have been shown to possess enhanced stemness properties (self-renewal and multipotency). So far though, not much is known about ALDH activity in specific fetal organs. In this study, we sought to analyze the presence and activity of the ALDH enzyme in the stem cell antigen-1-positive (Sca-1+) cells of fetal human heart. Biochemical assays showed that a subpopulation of Sca-1+ cells (15%) possess significantly high ALDH1 activity. This subpopulation showed increased expression of self-renewal markers compared to the ALDH(low) fraction. The ALDH(high) fraction also exhibited significant increase in proliferation and pro-survival gene expression. In addition, only the ALDH(high) and not the ALDH(low) fraction could give rise to all the cell types of the original population, demonstrating multipotency. ALDH(high) cells showed increased resistance against aldehyde challenge compared to ALDH(low) cells. These results indicate that ALDH(high) subpopulation of the cultured human fetal cells has enhanced self-renewal, multipotency, high proliferation, and survival, indicating that this might represent a primitive stem cell population within the fetal human heart.

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Analysis of the potential of ALDHhigh and ALDHlow Sca-1+ cells to recapitulate the original population. (a) Representation of flow cytometric analysis of ALDHhigh Sca-1+ cells (left panel) and ALDHlow Sca-1+ cells (right panel) one week after in vitro culture. (b) Graphical representation of the percentage of ALDHhigh Sca-1+ cells in the original population, arising from ALDHhigh Sca-1+ cells and ALDHlow Sca-1+ cells. (n = 3; *P value < 0.001).
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fig5: Analysis of the potential of ALDHhigh and ALDHlow Sca-1+ cells to recapitulate the original population. (a) Representation of flow cytometric analysis of ALDHhigh Sca-1+ cells (left panel) and ALDHlow Sca-1+ cells (right panel) one week after in vitro culture. (b) Graphical representation of the percentage of ALDHhigh Sca-1+ cells in the original population, arising from ALDHhigh Sca-1+ cells and ALDHlow Sca-1+ cells. (n = 3; *P value < 0.001).

Mentions: In order to test the potential of ALDHhigh and ALDHlow Sca-1+ cells to give rise to all the cell types existing in the original population from which they were derived, the two populations were cultured. After two weeks in culture, both populations were subject to the Aldefluor assay to determine ALDH activity. While the ALDHlow Sca-1+ cells could only give rise to ALDHlow subpopulation (>97%; P value < 0.05) (Figure 5), the ALDHhigh Sca-1+ cells recapitulated the original population by giving rise to both the ALDHhigh and ALDHlow populations, in addition to maintaining a high percentage of the cells with ALDHhigh phenotype. This was consistently observed for multiple samples, and this observation held true even after 2-3 weeks of culture.


Sca-1+ cells from fetal heart with high aldehyde dehydrogenase activity exhibit enhanced gene expression for self-renewal, proliferation, and survival.

Dey D, Pan G, Varma NR, Palaniyandi SS - Oxid Med Cell Longev (2015)

Analysis of the potential of ALDHhigh and ALDHlow Sca-1+ cells to recapitulate the original population. (a) Representation of flow cytometric analysis of ALDHhigh Sca-1+ cells (left panel) and ALDHlow Sca-1+ cells (right panel) one week after in vitro culture. (b) Graphical representation of the percentage of ALDHhigh Sca-1+ cells in the original population, arising from ALDHhigh Sca-1+ cells and ALDHlow Sca-1+ cells. (n = 3; *P value < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4377537&req=5

fig5: Analysis of the potential of ALDHhigh and ALDHlow Sca-1+ cells to recapitulate the original population. (a) Representation of flow cytometric analysis of ALDHhigh Sca-1+ cells (left panel) and ALDHlow Sca-1+ cells (right panel) one week after in vitro culture. (b) Graphical representation of the percentage of ALDHhigh Sca-1+ cells in the original population, arising from ALDHhigh Sca-1+ cells and ALDHlow Sca-1+ cells. (n = 3; *P value < 0.001).
Mentions: In order to test the potential of ALDHhigh and ALDHlow Sca-1+ cells to give rise to all the cell types existing in the original population from which they were derived, the two populations were cultured. After two weeks in culture, both populations were subject to the Aldefluor assay to determine ALDH activity. While the ALDHlow Sca-1+ cells could only give rise to ALDHlow subpopulation (>97%; P value < 0.05) (Figure 5), the ALDHhigh Sca-1+ cells recapitulated the original population by giving rise to both the ALDHhigh and ALDHlow populations, in addition to maintaining a high percentage of the cells with ALDHhigh phenotype. This was consistently observed for multiple samples, and this observation held true even after 2-3 weeks of culture.

Bottom Line: The ALDH(high) fraction also exhibited significant increase in proliferation and pro-survival gene expression.ALDH(high) cells showed increased resistance against aldehyde challenge compared to ALDH(low) cells.These results indicate that ALDH(high) subpopulation of the cultured human fetal cells has enhanced self-renewal, multipotency, high proliferation, and survival, indicating that this might represent a primitive stem cell population within the fetal human heart.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA ; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

ABSTRACT
Stem/progenitor cells from multiple tissues have been isolated based on enhanced activity of cytosolic aldehyde dehydrogenase (ALDH) enzyme. ALDH activity has emerged as a reliable marker for stem/progenitor cells, such that ALDH(bright/high) cells from multiple tissues have been shown to possess enhanced stemness properties (self-renewal and multipotency). So far though, not much is known about ALDH activity in specific fetal organs. In this study, we sought to analyze the presence and activity of the ALDH enzyme in the stem cell antigen-1-positive (Sca-1+) cells of fetal human heart. Biochemical assays showed that a subpopulation of Sca-1+ cells (15%) possess significantly high ALDH1 activity. This subpopulation showed increased expression of self-renewal markers compared to the ALDH(low) fraction. The ALDH(high) fraction also exhibited significant increase in proliferation and pro-survival gene expression. In addition, only the ALDH(high) and not the ALDH(low) fraction could give rise to all the cell types of the original population, demonstrating multipotency. ALDH(high) cells showed increased resistance against aldehyde challenge compared to ALDH(low) cells. These results indicate that ALDH(high) subpopulation of the cultured human fetal cells has enhanced self-renewal, multipotency, high proliferation, and survival, indicating that this might represent a primitive stem cell population within the fetal human heart.

Show MeSH