New class of genetic switches gives clues about the development of stem cells
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The Case Western Reserve researchers found landmarks in pluripotent stem cells that guide how they develop to serve different purposes in the body. This promising breakthrough that scientists will eventually be able to direct stem cells to prevent disease or to repair damage from an injury or illness. The study and its results are published in the June 5 edition of the journal Cell Stem.
Pluripotent stem cells are so named because they can evolve into one of the cell types that exist in the body. Their immense potential has attracted the attention of two teachers accomplished with complementary expertise.
"We had a unique opportunity to bring together two interdisciplinary groups," said co-author Paul Tesar, PhD, Assistant Professor of Genetics and Genome Sciences at CWRU School of Medicine and Dr. Donald and Ruth Weber Goodman Professor.
"We tapped the expertise of Tesar lab stem cell biology and expertise of my laboratory genomics to discover a new class of genetic switches, we call seed enhancers "said co-lead author Peter Scacheri, PhD, Associate Professor of Genetics and Genome Sciences at CWRU School of Medicine. . "Seed enhancers give us new clues about how cells transform from one cell type to another during development"
The breakthrough came from studying two types of cells closely related strains that represent the early stages of development - embryonic stem cells and stem cells epiblast, first described in research by Tesar in 07. "These two types of stem cells give us unprecedented access to early development mammals, "said Daniel Factor, graduate student in the Tesar lab and co-first author of the study.
Olivia Corradin, graduate student in the Scacheri laboratory and co-first author, agrees . "stem cells are touted for their promise to make replacement tissues for regenerative medicine," she said. "But first, we need to understand exactly how these cells work to create a variety of tissues."
Enhancers are DNA sections that control the expression of neighboring genes. By comparing these two types of pluripotent stem cells (embryonic and epiblast) closely related, Corradin and factor identified a new class of activators, which they refer as seed enhancers. Unlike most amplifiers, which are active only in the time or specific locations in the body, the seed enhancers play a role before birth to adulthood.
They are present but dormant, in mice early embryonic stem cell population. In the population of epiblast mouse stem cells more developed, they become the primary enhancers their associated genes. As mature cells in adult functional fabrics, seeds enhancers develop into super enhancers. Super activators are large areas that contain many amplifiers and control the most important genes in each cell type.
"These seeds enhancers have great potential to influence the development and understanding of the disease," said Stanton Gerson, MD, Asa & Patricia Shiverick and Jane Shiverick (Tripp) Professor of Hematology Oncology and director of the National Center for regenerative medicine at Case Western Reserve University. "in the field of stem cells, this understanding should quickly improve the ability to generate clinically useful cell types for regenerative medicine based on stem cells."
"Our next step is to understand that bad regulation of these seeds enhancers could play a role in human disease," said Tesar. "The genes controlled by seed enhancers are powerful, and it is possible that the aberrations can contribute to things like heart disease or neurodegenerative diseases."
Scacheri added, "It is also clear that cancer can be caused by changes in amplifiers, and we are interested in understanding the role of seed enhancers in cancer development and progression."
Case Western Reserve University research team discovered "seeds" of stem cell development
Pluripotent stem cells are so named because they can evolve into one of the cell types that exist in the body. Their immense potential has attracted the attention of two teachers accomplished with complementary expertise.
"We had a unique opportunity to bring together two interdisciplinary groups," said co-author Paul Tesar, PhD, Assistant Professor of Genetics and Genome Sciences at CWRU School of Medicine and Dr. Donald and Ruth Weber Goodman Professor.
"We tapped the expertise of Tesar lab stem cell biology and expertise of my laboratory genomics to discover a new class of genetic switches, we call seed enhancers "said co-lead author Peter Scacheri, PhD, Associate Professor of Genetics and Genome Sciences at CWRU School of Medicine. . "Seed enhancers give us new clues about how cells transform from one cell type to another during development"
The breakthrough came from studying two types of cells closely related strains that represent the early stages of development - embryonic stem cells and stem cells epiblast, first described in research by Tesar in 07. "These two types of stem cells give us unprecedented access to early development mammals, "said Daniel Factor, graduate student in the Tesar lab and co-first author of the study.
Olivia Corradin, graduate student in the Scacheri laboratory and co-first author, agrees . "stem cells are touted for their promise to make replacement tissues for regenerative medicine," she said. "But first, we need to understand exactly how these cells work to create a variety of tissues."
Enhancers are DNA sections that control the expression of neighboring genes. By comparing these two types of pluripotent stem cells (embryonic and epiblast) closely related, Corradin and factor identified a new class of activators, which they refer as seed enhancers. Unlike most amplifiers, which are active only in the time or specific locations in the body, the seed enhancers play a role before birth to adulthood.
They are present but dormant, in mice early embryonic stem cell population. In the population of epiblast mouse stem cells more developed, they become the primary enhancers their associated genes. As mature cells in adult functional fabrics, seeds enhancers develop into super enhancers. Super activators are large areas that contain many amplifiers and control the most important genes in each cell type.
"These seeds enhancers have great potential to influence the development and understanding of the disease," said Stanton Gerson, MD, Asa & Patricia Shiverick and Jane Shiverick (Tripp) Professor of Hematology Oncology and director of the National Center for regenerative medicine at Case Western Reserve University. "in the field of stem cells, this understanding should quickly improve the ability to generate clinically useful cell types for regenerative medicine based on stem cells."
"Our next step is to understand that bad regulation of these seeds enhancers could play a role in human disease," said Tesar. "The genes controlled by seed enhancers are powerful, and it is possible that the aberrations can contribute to things like heart disease or neurodegenerative diseases."
Scacheri added, "It is also clear that cancer can be caused by changes in amplifiers, and we are interested in understanding the role of seed enhancers in cancer development and progression."
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