Stem Cells and iPSCs

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Questions and Answers

What is the origin of iPSCs?

iPSCs are artificially derived from a non-pluripotent cell, typically an adult somatic cell, by inducing a 'forced' expression of certain genes.

What are the three groups of genes responsible for pluripotency in iPSCs?

The three groups of genes are: ES cell-Specific transcription factors, Proto-oncogenes, and Less famous genes.

What is the function of Oct3/4 in pluripotent cells?

Oct3/4 is involved in the maintenance of self-renewal of pluripotent cells.

What is the role of Sox2 in embryonic development?

Sox2 is essential for embryonic development. Signup and view all the answers

How does KIf4 regulate p53 and Nanog?

KIf4 represses p53 directly, which in turn contributes to the activation of Nanog and other ES cell-specific genes. Signup and view all the answers

What is the antiproliferation function of KIf4?

KIf4 activates p21CIP, thereby suppressing cell proliferation. Signup and view all the answers

What is the role of Nanog in embryonic stem cells?

Nanog, along with Oct-3/4 and Sox2, is necessary in promoting pluripotency. Signup and view all the answers

What is the function of LIN28 in embryonic stem cells?

LIN28 is an mRNA binding protein expressed in embryonic stem cells and embryonic carcinoma cells, associated with differentiation and proliferation. Signup and view all the answers

What is the purpose of using a reporter gene and antibiotic selection in the production of iPS cells?

To isolate transfected cells. Signup and view all the answers

What is the typical method used to achieve transfection in the production of iPS cells?

Viral vectors, such as retroviruses. Signup and view all the answers

What were the four key pluripotency genes used to generate the first generation of iPS cells?

Oct-3/4, Sox2, c-Myc, and Klf4. Signup and view all the answers

Who is credited with the first generation of iPS cells in 2006?

Shinya Yamanaka's team at Kyoto University, Japan. Signup and view all the answers

What was the limitation of the first generation of iPS cells?

DNA methylation errors compared to original patterns in ESC lines and failed to produce viable chimeras if injected into developing embryos. Signup and view all the answers

What was the improvement in the second generation of iPS cells in mice?

The use of Nanog instead of Fbx15, which resulted in correct DNA methylation patterns and production of viable chimeras. Signup and view all the answers

What is the role of Nanog in ESCs?

Nanog is an important gene in ESCs and a major determinant of cellular pluripotency. Signup and view all the answers

What is the limitation of using c-Myc in the production of iPS cells?

c-Myc is an oncogenic gene, which can lead to tumor formation. Signup and view all the answers

Study Notes

What are iPSCs

iPSCs (induced pluripotent stem cells) are a type of pluripotent stem cell artificially derived from a non-pluripotent cell, typically an adult somatic cell, by inducing a "forced" expression of certain genes.
First produced in 2006 from mouse cells and in 2007 from human cells.

Genes Responsible for Pluripotency

Group 1: ES cell-specific transcription factors, essential for pluripotency in ES cells and early embryos, including Oct3/4, Sox2, and Nanog.
Group 2: Proto-oncogenes, important for proliferation of ES cells, but not in early embryos, including TCLI, Stat3, c-Myc, and ERas.
Group 3: Less famous genes, specifically expressed in ES cells, but with less defined functions, including ECATI, Esg1, and Fbx15.

Key Functions of Genes

Oct3/4: involved in the maintenance of self-renewal of pluripotent cells, repression leads to formation of trophoectoderm, and overexpression leads to formation of various lineages, including primitive endoderm.
Sox2: essential for embryonic development, downregulation leads to differentiation of cells in murine ES cells.
KIf4: represses p53 directly, contributes to activation of Nanog and other ES cell-specific genes, acts as an inhibitor of c-Myc-induced apoptosis, and activates p21CIP, thereby suppressing cell proliferation.
Nanog: necessary for promoting pluripotency in embryonic stem cells, along with Oct-3/4 and Sox2.
LIN28: an mRNA binding protein expressed in embryonic stem cells and embryonic carcinoma cells, associated with differentiation and proliferation.

Production of iPSCs

Typically derived by transfecting certain stem cell-associated genes into non-pluripotent cells, such as adult fibroblasts, using viral vectors, such as retroviruses.
Small numbers of transfected cells become morphologically and biochemically similar to pluripotent stem cells, and are isolated through morphological selection, doubling time, or through a reporter gene and antibiotic selection.

First Generation of iPSCs

First generated by Shinya Yamanaka's team at Kyoto University, Japan in 2006, using four key pluripotency genes: Oct-3/4, Sox2, c-Myc, and KIf4.
Retroviruses were used to transfect mouse fibroblasts, and cells were isolated by antibiotic selection of Fbx15+ cells.
Limitations: DNA methylation errors compared to original patterns in ESC lines and failed to produce viable chimeras if injected into developing embryos.

Second Generation of iPSCs in Mice

Generated in June 2007, by the same group, using the same four endogenous pluripotent factors, but with Nanog instead of Fbx15.
DNA methylation patterns and producing viable chimeras indicated that Nanog is a major determinant of cellular pluripotency.
Limitations: one of the four genes used (c-Myc) is oncogenic, and 20% of the chimeric mice developed tumors.

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Description

This quiz covers induced pluripotent stem cells (iPSCs), their derivation from adult somatic cells, and the genes responsible for pluripotency. It also touches on the differences between ES cells and iPSCs.