Embryonic Stem Cells

Publication Title: 
Aging

Very small embryonic-like stem cells (VSELs) are a population of developmentally early stem cells residing in adult tissues. These rare cells, which are slightly smaller than red blood cells, i) become mobilized during stress situations into peripheral blood, ii) are enriched in the Sca1+Lin-CD45- cell fraction in mice and the CD133+ Lin-CD45- cell fraction in humans, iii) express markers of pluripotent stem cells (e.g., Oct4, Nanog, and SSEA), and iv) display a distinct morphology characterized by a high nuclear/cytoplasmic ratio and undifferentiated chromatin.

Author(s): 
Ratajczak, Mariusz Z.
Shin, Dong-Myung
Liu, Rui
Mierzejewska, Kasia
Ratajczak, Janina
Kucia, Magda
Zuba-Surma, Ewa K.
Publication Title: 
Nature

Embryonic stem cells can replicate continuously in the absence of senescence and, therefore, are immortal in culture. Although genome stability is essential for the survival of stem cells, proteome stability may have an equally important role in stem-cell identity and function. Furthermore, with the asymmetric divisions invoked by stem cells, the passage of damaged proteins to daughter cells could potentially destroy the resulting lineage of cells. Therefore, a firm understanding of how stem cells maintain their proteome is of central importance.

Author(s): 
Vilchez, David
Boyer, Leah
Morantte, Ianessa
Lutz, Margaret
Merkwirth, Carsten
Joyce, Derek
Spencer, Brian
Page, Lesley
Masliah, Eliezer
Berggren, W. Travis
Gage, Fred H.
Dillin, Andrew
Publication Title: 
Aging Cell

Proteostasis is critical for maintaining cell function and proteome stability may play an important role in human embryonic stem cell (hESC) immortality. Notably, hESC populations exhibit a high assembly of active proteasomes, a key node of the proteostasis network. FOXO4, an insulin/IGF-1 responsive transcription factor, regulates proteasome activity in hESCs. We find that loss of FOXO4 reduces the potential of hESCs to differentiate into neural lineages. Therefore, FOXO4 crosses evolutionary boundaries and links hESC function to invertebrate longevity modulation.

Author(s): 
Vilchez, David
Boyer, Leah
Lutz, Margaret
Merkwirth, Carsten
Morantte, Ianessa
Tse, Chris
Spencer, Brian
Page, Lesley
Masliah, Eliezer
Berggren, William Travis
Gage, Fred H.
Dillin, Andrew
Publication Title: 
Molecular Cell

Histone H3K4 demethylase LSD1 plays an important role in stem cell biology, especially in the maintenance of the silencing of differentiation genes. However, how the function of LSD1 is regulated and the differentiation genes are derepressed are not understood. Here, we report that elimination of LSD1 promotes embryonic stem cell (ESC) differentiation toward neural lineage. We showed that the destabilization of LSD1 occurs posttranscriptionally via the ubiquitin-proteasome pathway by an E3 ubiquitin ligase, Jade-2.

Author(s): 
Han, Xiao
Gui, Bin
Xiong, Cong
Zhao, Linnan
Liang, Jing
Sun, Luyang
Yang, Xiaohan
Yu, Wenhua
Si, Wenzhe
Yan, Ruorong
Yi, Xia
Zhang, Di
Li, Wanjin
Li, Lifang
Yang, Jianguo
Wang, Yan
Sun, Yi Eve
Zhang, Dai
Meng, Anming
Shang, Yongfeng
Publication Title: 
International Journal of Oncology

Metastatic chondrosarcoma of mesenchymal origin is the second most common bone malignancy and does not respond either to chemotherapy or radiation; therefore, the search for new therapies is relevant and urgent. We described recently that tumor growth inhibiting cytostatic proline-rich polypeptide 1, (PRP-1) significantly upregulated tumor suppressor miRNAs, downregulated onco-miRNAs in human chondrosarcoma JJ012 cell line, compared to chondrocytes culture.

Author(s): 
Galoian, Karina
Qureshi, Amir
D'Ippolito, Gianluca
Schiller, Paul C.
Molinari, Marco
Johnstone, Andrea L.
Brothers, Shaun P.
Paz, Ana C.
Temple, H. T.
Publication Title: 
Journal International De Bioethique = International Journal of Bioethics

While medicine has made remarkable progress over the last decades, its development has also raised numerous ethical and legal issues. In this context, the question arises as to what framework is needed for research, organ transplants, and medically assisted reproduction. A balance has to be found between scientific freedom, the imperatives of public health and the protection of people ' welfare, rights and human dignity. Those questions have led to the adoption of multiple national laws as well as ethical and legal norms at the international level.

Author(s): 
Sprumont, Dominique
Roduit, Guillaume
Hertig Pea, AgnËs
Publication Title: 
Modern Healthcare

When a federal judge ruled last week to close off millions of dollars in federal funding for human embryonic stem-cell studies, researchers across the country cringed. "It will stop bright, young people from going into this field because they'll see their careers being threatened," says Richard Hynes, a professor at MIT. However, some organizations, such as the Catholic Health Association, welcomed the decision.

Author(s): 
Zigmond, Jessica
Publication Title: 
Fertility and Sterility

OBJECTIVE: To review publications regarding possible donation of surplus embryos for medical research. DESIGN: Review of 67 scientific publications in this field up through January 2007. ORIGINALITY: Summary of factors influencing prospective donors' motivation to donate or not donate their surplus embryos for medical research.

Author(s): 
Hug, Kristina
Publication Title: 
Human Fertility (Cambridge, England)

An Ethics & Policy Workshop was held with 20 invited UK stakeholders to consider whether embryo donors should be able to restrict the future use of human embryonic stem cells (hESCs) created from their embryos. Participants cited tensions between pure altruism and a more reciprocal basis for donation; and between basic research (in which genetic material would never form part of another living being) and treatment applications.

Author(s): 
Ehrich, Kathryn
Farsides, Bobbie
Williams, Clare
Scott, Rosamund
Publication Title: 
Stem Cells (Dayton, Ohio)

Human embryonic stem cells (hESCs) have been reported to exert cytoprotective activity in the area of tissue injury. However, hypoxia/oxidative stress prevailing in the area of injury could activate p53, leading to death and differentiation of hESCs. Here we report that when exposed to hypoxia/oxidative stress, a small fraction of hESCs, namely the SSEA3+/ABCG2+ fraction undergoes a transient state of reprogramming to a low p53 and high hypoxia inducible factor (HIF)-2? state of transcriptional activity.

Author(s): 
Das, Bikul
Bayat-Mokhtari, Reza
Tsui, Micky
Lotfi, Shamim
Tsuchida, Rika
Felsher, Dean W.
Yeger, Herman

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