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Related Concept Videos

Embryonic Stem Cells00:58

Embryonic Stem Cells

Embryonic stem (ES) cells are undifferentiated pluripotent cells, meaning they can produce any cell type in the body. This gives them tremendous potential in science and medicine since they can generate specific cell types for use in research or to replace body cells lost due to damage or disease.
Embryonic Stem Cells00:57

Embryonic Stem Cells

Embryonic stem (ES) cells were first discovered in mice in 1981 by Martin Evans. In 1998, James Thomson identified a method to isolate embryonic stem cells from humans. Human embryonic stem cells (hESCs) are obtained from 3-5 day old embryos that remain unused after an in vitro fertilization procedure.
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...
Induced Pluripotent Stem Cells01:13

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore called induced pluripotent stem...
In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
Zygotic Development And Stem Cell Formation01:10

Zygotic Development And Stem Cell Formation

The development of all multicellular organisms starts with the fusion of haploid cells called sperm and egg to form a diploid zygote. A zygote is a totipotent cell that can develop into a complete organism. The zygote undergoes cell division or cleavage to form an 8-cell mass. Until this stage, the cells are spherical, loosely attached, and remain totipotent. Totipotent cells are capable of developing both the embryonic and the extraembryonic tissues. However, as they continue to divide, they...
Methods of Nuclear Reprogramming01:24

Methods of Nuclear Reprogramming

Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for injury repair.

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CRISPR-Cas9 Mediated Gene Deletion in Human Pluripotent Stem Cells Cultured Under Feeder-Free Conditions
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KCNJ11 knockout morula re-engineered by stem cell diploid aggregation.

Timothy J Nelson1, Almudena Martinez-Fernandez, Andre Terzic

  • 1Departments of Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA.

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
|November 4, 2008
PubMed
Summary
This summary is machine-generated.

Researchers created KCNJ11 KATP channel knockout-wild-type chimeras to study stress responses. This new method allows examination of how genetic variations influence stress intolerance during development.

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Area of Science:

  • Physiology
  • Genetics
  • Molecular Biology

Background:

  • ATP-sensitive K+ (KATP) channels, formed by KCNJ11-encoded Kir6.2 and sulfonylurea receptors, regulate cellular functions based on energy demand.
  • Genetic defects in KATP channels lead to maladaptation and organ dysfunction, particularly in stress-related conditions (KATP channelopathies).

Purpose of the Study:

  • To develop a novel platform for investigating the role of genetic variation in KATP channel function and stress response during development.
  • To assess the contribution of genetic variance to stress intolerance using a chimera model.

Main Methods:

  • Engineered KCNJ11 KATP channel gene knockout<-->wild-type chimeras via diploid aggregation.
  • Integrated wild-type embryonic stem cells into knockout morulae to create mosaic embryos.
  • Utilized ex vivo derived mosaic blastocysts for intrauterine transfer and full-term development in pseudopregnant surrogates.

Main Results:

  • Mosaic blastocysts derived from knockout<-->wild-type embryos successfully implanted and developed to term, producing live chimeric offspring.
  • The study demonstrated the feasibility of generating viable chimeras with varying degrees of stress-tolerant tissue integration.
  • Adult chimerism was achieved from mosaic embryos, showcasing the potential of this model.

Conclusions:

  • The development of KATP channel knockout<-->wild-type chimeras provides a new paradigm for studying ecogenetic control of stress response.
  • This chimera model enables the examination of adaptive behaviors influenced by genetic factors in KATP channelopathies.
  • The findings highlight the potential of chimeras to probe developmental impacts of genetic variations on organ tolerance and stress adaptation.