HSCI Science Update: April 2010

April 30, 2010

One of These Things is Not Like the Other…and Provides Clues to Developmental Potential

Since induced pluripotent stem (iPS) cells were first introduced just a few years ago, their equivalence to embryonic stem cells has not been entirely ascertained. In order to address this question, HSCI Principal Faculty member Konrad Hochedlinger and fellow researchers studied genetically identical mouse embryonic stem cells and iPS cells. They found that the RNA expressed by the two different types of cells was almost identical with the exception of one particular gene cluster that was not expressed in the iPS cells. Interestingly, consistent with a role for these silenced genes in development, those iPS cells in which the cluster was silenced developed into animals poorly, while those in which it was not silenced developed well. Furthermore, when the cells with the silenced cluster were treated with factors that activated the cluster, the cells then developed well. These results are exciting because they suggest a great degree of similarity between iPS and ES cells, which make iPS cells a potentially instructive tool and model for helping researchers understand injury and disease. Also, the identification of a particular gene cluster associated with iPS cells that have the developmental potential of ES cells provides researchers with a helpful assay to determine which iPS cells to work with in order to obtain full developmental potential.

Stadtfeld, M., Apostolou, E., Akutsu, H., Fukuda, A., Follett, P., Natesan, S., Kono, T., Shioda, T., Hochedlinger, K. (2010). Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells. Nature Apr 25. [Epub ahead of print]

It Takes More Than Just Nerves To Get Your Message Across

In addition to forming neurons, developing neural tissue also forms glial cells, which provide a number of functions including forming the protective myelin sheaths around the neurons, providing structural support to the neurons, as well as delivering nutrients and oxygen to the neurons. The lineage of the different glial cell types that provide these functions has not been fully elaborated for many areas of the nervous system. In order to understand the relationship and lineage of the glial cells, HSCI Principal Faculty member Constance Cepko and a fellow researcher tagged glial cells in the developing chick retina. They found that almost every glial cell clone also had astrocytes, cells that anchor neurons to their blood supply and regulate their chemical environment, and oligodendrocytes, the cells that make up the myelin that insulates neurons and helps electrical signals propagate. These findings suggest that the two glial cell types have a common progenitor. Additionally, the researchers identified an additional intermediate cell type that also shares a progenitor with astrocytes and oligodendrocytes. This increased understanding of the lineage is particularly exciting in light of advances in directed differentiation studies that are informed by knowledge of lineage-specific factors, allowing researchers to potentially generate these cell types to treat injury and disease.

Rompani, S.B., Cepko, C.L. (2010). A common progenitor for retinal astrocytes and oligodendrocytes. J Neurosci. 30, 4970-80.

Role for Wnt/beta-catenin Pathway in Leukemia Stem Cell Self-Renewal

Leukemia is maintained by leukemia stem cells (LSCs) that are capable of unlimited self-renewal. The ability to selectively destroy these LSCs would be a powerful therapeutic approach. In order to better understand how the LSCs are regulated, HSCI Principal Faculty member Scott Armstrong and colleagues studied the genetic pathways involved in self-renewal of LSCs in mouse models of acute myelogenous leukemia (AML) and found that the Wnt/beta-catenin pathway was required for self-renewal in LSCs derived from hematopoietic stem cells (HSCs) and another cell type called the granulocyte-macrophage progenitors, but is not required for self-renewal in normal adult HSCs. These finding suggest that targeting the Wnt/beta-catenin pathway may represent an exciting therapeutic approach for the treatment of AML.

Wang, Y., Krivtsov, A.V., Sinha, A.U., North, T.E., Goessling, W., Feng, Z., Zon, L.I., Armstrong, S.A. (2010). The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML. Science 327, 1650-3.