title: Sca-1+ cells from fetal heart with high aldehyde dehydrogenase activity exhibit enhanced gene expression for self-renewal, proliferation, and survival.
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.
authors: 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.
authors: Devaveena
authors: D
authors: Dey
authors: Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, USA.
authors: Guodong
authors: G
authors: Pan
authors: Cellular and Molecular Imaging Laboratory, Department of Radiology, Henry Ford Health System, Detroit, MI 48202, USA.
authors: Nadimpalli Ravi S
authors: NR
authors: Varma
authors: Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, USA ; Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA ; Department of Physiology, Wayne State University, Detroit, MI 48202, USA.
authors: Suresh Selvaraj
authors: SS
authors: Palaniyandi
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D049109:Cell Proliferation; D005318:Fetal Heart / Q000166:cytology*; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D018189:Immunomagnetic Separation; D019394:Ki-67 Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D050697:Retinal Dehydrogenase; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase