In 2006, scientists demonstrated that inserting four embryonic genes into mouse skin cells induced a small fraction of them to look and behave like embryonic stem cells.

Konrad Hochedlinger, an assistant professor of medicine at Harvard Medical School, found a simple way to improve the technique. Working with mouse cells, he initiated the reprogramming process by means of the same four genes that previous scientists had used. But he used a different gene to identify the cells that had been successfully reprogrammed; cells in which that gene is active turn out to look and act more like embryonic stem cells than those made previously. The technique offers a way around the controversies that have slowed embryonic-stem-cell research, which has the potential to help scientists understand certain diseases and, eventually, replace diseased or damaged tissue.

Research Interests

Our lab tries to understand the role stem cells play in normal development and disease. Stem cells have the dual potential to self-renew and give rise to differentiated cells. They play key roles in normal development, during tissue homeostasis and following injury in the adult. Moreover, stem cells have been experimentally shown to be the cells of origin in certain types of cancer. To understand the biology of stem cells and to exploit their use for therapy, it is critical to identify and characterize the factors that control the decision between their self-renewal and differentiation under normal physiological conditions and in disease.

We are particularly interested in the biology of embryonic stem (ES) cells which are the only cell type that retains pluripotentiality. The pluripotent state of ES cells is maintained by a set of transcription factors including Oct4, Sox2 and Nanog. Genetic studies have shown that Oct4 and Nanog keep ES cells undifferentiated by inhibiting their differentiation into trophectoderm and endoderm, respectively. Interestingly, some of these factors appear to be important also in other cell types such as neural stem cells as well as in different biological processes, such as nuclear reprogramming. We have recently generated pluripotent cells from fibroblasts by ectopic expression of the trancription factors Oct4, Sox2, c-myc and Klf4. These cells show global epigenetic remodeling, reactivation of a silenced X chromosome and broad contribution to chimeric animals including female germ cells.

We are using in vitro and in vivo model systems to further characterize the role of pluripotency genes in stem cell self-renewal, reprogramming and cancer. Specifically, future projects will include (i) the screening for novel genes involved in the self-renewal of stem cells and (ii) their analysis in normal development and cancer by establishing novel mouse models, and (iii) nuclear reprogramming of mouse and human cells by defined factors.

Hochedlinger's Research Group

Hochedlinger's Publications

1:

Epigenetic reprogramming and induced pluripotency.

Hochedlinger K, Plath K.

Development. 2009 Feb;136(4):509-23.

PMID: 19168672 [PubMed - in process]

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