Welcome to Stem Cell School

Stem Cell School is an educational website designed for high school and undergraduate level life-science educators. The unique educational content found on this site was developed collaboratively with award winning high school educators, international stem cell organizations and professional medical animators--creating dynamic and engaging educational resources that teach pertinent cellular biology topics through the lens of stem cells and cellular reprogramming.

This lesson on cellular reprogramming is Stem Cell School's pilot project and the first of a series of lessons that will teach the science and application of stem cell biology and regenerative medicine. Stem Cell School's first lesson covers the topic of cellular reprogramming and the creation of induced pluripotent stem cells.

This lesson may be used to supplement the teaching of:

• gene regulation
• gene transcription and protein translation
• biotechnology
• genetic engineering and transgenics
• developmental biology and epigenetics
• viral infection and replication

Lesson 1: Cellular Reprogramming and the Creation of Induced Pluripotent Stem Cells: From Dolly to iPS

There are many different types of stem cells within our body. Each type of stem cell is defined by the group of specialized cells it gives rise to. However, there are two fundamental properties that distinguish all stem cells, including induced pluripotent stem cells, from other somatic cells: self-renewal and potency.

Like totipotent stem cells, pluripotent stem cells also contain the capacity to become all cells of the developed organism but cannot produce trophoblast and placenta to support uterus implantation and organismal development. Pluripotent embryonic stem (ES) cells are found within the inner cell mass of the blastocyst approximately 3-5 days post fertilization. Pluripotent embryonic stem cells of the inner cell mass have been successfully extracted, isolated and cultured to produce embryonic stem cell lines. These pluripotent cells have the natural capacity to differentiate into all germ layers and cell types; however, under normal developmental conditions these cells cannot revert to the pluripotent state once committed to a specific cell lineage. To this end, cell development has been viewed as a unidirectional process in which cells continue to differentiate into mature specialized cells.

This hypothesis that cells only differentiate unidirectionally towards terminal differentiation was challenged in 1962 by John Gurdon's pioneering work in nuclear transfer and also with the historic birth of Dolly the Sheep in February of 1996 via somatic cell nuclear transfer (SCNT). Somatic cell nuclear transfer or SCNT, entails injection of a nucleus from a somatic cell into an enucleated oocyte to form a pluripotent cell capable of developing into an entire organism. The success of SCNT stimulated developmental biologists to begin exploring the possibility of creating pluripotent stem cells (e.g. induced pluripotent stem cells) through cellular reprogramming of fully differentiated somatic cells.

The groundbreaking discovery came in 2006 when Kazutoshi Takahashi and Shinya Yamanaka demonstrated that mouse fibroblasts can be reprogrammed to pluripotent, "embryonic like" stem cells, by overexpressing genetic factors. The team hypothesized that a select group of 24 pluripotency related genes, when over-expressed in mouse somatic cells can induce pluripotency. Of the 24 genes screened, only 4 were necessary to reprogram mouse fibroblasts into pluripotent stem cells—otherwise known as iPS cells. The Yamanaka team determined the essential reprogramming genes to be Oct-4, SOX2, Klf-4 and c-Myc, four genes that have important function in the regulation of pluripotency in embryonic stem cells. One year later, the team reported that the same four factors are capable of inducing pluripotency in human somatic cells. This discovery revolutionized the field of stem cell science and regenerative medicine as it opened the door for creation of patient specific autologous pluripotent stem cells. Today, stem cell scientists are looking to reprogram cells using small molecules and other safer technologies to hopefully one-day use iPS technology in clinical cell therapies.