Concise Review: Stem Cell Antigen-1: Expression, Function, and Enigma

Holmes, Christina; Stanford, William L.

doi:10.1634/stemcells.2006-0644

Cited by 362 publications

(342 citation statements)

References 126 publications

(166 reference statements)

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“…Previous studies demonstrated that Thy1 expression defines lipofibroblastic or myofibroblastic lineage, 26 while Sca1 is a marker specifying murine mesenchymal and epithelial progenitor cells. 27 Our microarray analyses confirmed that Sca1-single-positive cells (SP) express genes broadly involved in embryonic and tissue morphogenesis, thus indicating their immature origin (Supplemental Table 1), whereas Thy1/Sca1-doublenegative (DN) cells selectively express markers of myofibroblast-committed progenitors (Supplemental Table 2). Notably, the Thy1-positive fractions (composed of Thy1-single positive (Thy1-SP) and Thy1/Sca1 double-positive (DP) cells) represent the majority of MEFs (470%), while Thy1-negative (Sca1-SP and DN) cells are a minority (10-15% each, Figure 1a).…”

Section: Resultssupporting

confidence: 52%

Two-factor reprogramming of somatic cells to pluripotent stem cells reveals partial functional redundancy of Sox2 and Klf4

et al. 2012

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Ectopic expression of defined sets of transcription factors in somatic cells enables them to adopt the qualities of pluripotency. Mouse embryonic fibroblasts (MEFs) are the classic target cell used to elucidate the core principles of nuclear reprogramming. However, their phenotypic and functional heterogeneity represents a major hurdle for mechanistic studies aimed at defining the molecular nature of cellular plasticity. We show that reducing the complexity of MEFs by flow cytometry allows the isolation of discrete cell subpopulations that can be efficiently reprogrammed to pluripotency with fewer genes. Using these FACS-sorted cells, we performed a systematic side-by-side analysis of the reprogramming efficiency with different two-and three-factor combinations of Oct4, Sox2 and Klf4. We show that introduction of exogenous Oct4 with either Sox2 or Klf4 does not directly convert MEFs to a pluripotent state. Instead, each combination of factors disrupts the normal cellular homeostasis and establishes transient states characterized by the concurrent expression of mixed lineage markers. These cells convert into induced pluripotent stem cells in a stochastic fashion. Our data suggest that there is a partial functional redundancy between Sox2 and Klf4 in the disruption of cellular homeostasis and activation of regulatory networks that define pluripotency. Reprogramming somatic cells into induced pluripotent stem (iPS) cells represents a valuable resource for the development of general and patient-specific therapies. The crucial issues facing the clinical translation of iPS technology are (i) choosing the most appropriate cell type for induction of pluripotency; (ii) improving the reprogramming efficiency; and (iii) gaining a mechanistic understanding of the reprogramming process. To date, multiple cell types have been used for iPS production, including embryonic and adult fibroblasts, adipocytes, cardiomyocytes, epithelial, vascular, hematopoietic and neuronal progenitors.

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Section: Resultssupporting

confidence: 52%

Two-factor reprogramming of somatic cells to pluripotent stem cells reveals partial functional redundancy of Sox2 and Klf4

et al. 2012

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“…18) Our results showed that large amounts of new CMs were generated in this process. However, we did not investigate the activation of cardiac stem cell-like populations, such as c-kit + , Sca1 + cells.6, [19][20][21] Studies have indicated that neonatal-derived cardiac stem cells have a strong regenerative ability when compared with adult-derived cardiac stem cells. 22,23) In our results, we also noticed that there are large numbers of CMs generated in the normal development of neonatal rat.…”

Section: Discussionmentioning

confidence: 99%

Ascending Aortic Constriction Promotes Cardiomyocyte Proliferation in Neonatal Rats

et al. 2017

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SummaryAdult heart suffering from increased workload will undergo myocardial hypertrophy, subsequent cardiomyocyte (CM) death, and eventually heart failure. However, the effect of increasing afterload on the neonatal heart remains unknown. We performed ascending aortic constriction (AAC) in neonatal rats 8-12 hours after birth (P0, P indicates postpartum). Seven days after surgery, in vivo heart function was evaluated using cardiac ultrasonography. Haematoxylineosin and Masson staining were used to assess CM diameter and collagen deposition. Moreover, expression of both EdU and Ki67 were evaluated to determine DNA synthesis levels, and pH3 and aurora B as markers for mitosis in CMs. CM isolation was performed by heart perfusion at P0, P3, P5, and P7, respectively. CM number on P0 was 1.01 ± 0.29 × 10 6 . We found that CM cell cycle activation was significantly increased among constricted hearts, as demonstrated by increased Ki67, EdU, pH3, and aurora B positive cells/1000 CMs. At day 7 (P7), constriction group hearts manifested increased wall thickness (0.55 ± 0.05 mm versus 0.85 ± 0.10 mm, P < 0.01, n = 6), and improved hemodynamics as well as left ventricular ejection fraction (65.5 ± 3.7% versus 77.7 ± 4.8%, P < 0.01, n = 6). Of note, the population of CMs was also markedly increased in the constriction group (2.92 ± 0.27 × 10 6 versus 3.41 ± 0.40 × 10 6 , P < 0.05, n = 6). In summary, we found that during the first week after birth significant numbers of neonatal CMs can reenter the cell cycle. Ascending aortic constriction promotes neonatal rat CM proliferation resulting in 16.7% more CMs in the heart. (Int Heart J 2017; 58: 264-270) Key words: Cell cycle reentry, Regeneration H eart failure is an increasing burden on health care systems around the world. 1) Many forms of heart diseases result in significant and permanent losses of functional cardiomyocytes (CMs), such as coronary artery disease and pressure-loading cardiomyopathies. Efforts to address this issue have led to the exploration of methods for CM regeneration even though the mammalian heart has long been considered a postmitotic organ. Recently, it was shown that individual CMs may be not as old as the person -almost 50% of CMs are replaced during a normal life span.2) By combining different genetic fate-mapping approaches, scientists have found that the genesis of CMs occurs by division of preexisting CMs.3,4) Although it happens at a very low rate, this evidence suggests that the heart is not terminally differentiated but instead an organ with regenerative potential. More lately, the discovery of an epimorphic regeneration potential in neonatal mammal hearts has contributed greatly to new insights in cardiac biology. In particular, neonatal mice can fully regenerate their heart after apex resection in a very short time.5) BrdU, pH3 labeling, and genetic fate-mapping have indicated that the majority of regenerated CMs originated from preexisting ones. A similar conclusion was obtained by another research group working on a different animal mode...

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“…While LY6A is frequently used to identify stem and progenitor cells in mouse, LY6A does not have a human homolog, restricting the use of this marker to murine studies (Holmes & Stanford 2007).…”

Section: Ly6amentioning

confidence: 99%

Epithelial ovarian cancer stem cells: underlying complexity of a simple paradigm

Garson¹,

Vanderhyden²

2015

Reproduction

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The lack of significant progress in the treatment of epithelial ovarian cancer (EOC) underscores the need to gain a better understanding of the processes that lead to chemoresistance and recurrence. The cancer stem cell (CSC) hypothesis offers an attractive explanation of how a subpopulation of cells within a patient's tumour might remain refractory to treatment and subsequently form the basis of recurrent chemoresistant disease. This review examines the literature defining somatic stem cells of the ovary and fallopian tube, two tissues that give rise to EOC. In addition, considerable research has been reviewed, that has identified subpopulations of EOC cells, based on marker expression (CD133, CD44, CD117, CD24, epithelial cell adhesion molecule, LY6A, ALDH1 and side population (SP)), which are enriched for tumour initiating cells (TICs). While many studies identified either CD133 or CD44 as markers useful for enriching for TICs, there is little consensus. This suggests that EOC cells may have a phenotypic plasticity that may preclude the identification of universal markers defining a CSC. The assay that forms the basis of quantifying TICs is the xenograft assay. Considerable controversy surrounds the xenograft assay and it is essential that some of the potential limitations be examined in this review. Highlighting such limitations or weaknesses is required to properly evaluate data and broaden our interpretation of potential mechanisms that might be contributing to the pathogenesis of ovarian cancer.

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Concise Review: Stem Cell Antigen-1: Expression, Function, and Enigma

Cited by 362 publications

References 126 publications

Two-factor reprogramming of somatic cells to pluripotent stem cells reveals partial functional redundancy of Sox2 and Klf4

Two-factor reprogramming of somatic cells to pluripotent stem cells reveals partial functional redundancy of Sox2 and Klf4

Ascending Aortic Constriction Promotes Cardiomyocyte Proliferation in Neonatal Rats

Epithelial ovarian cancer stem cells: underlying complexity of a simple paradigm

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