Stem Cells

In the breast, cancer stem cells and normal stem cells can arise from different cell types and tap into distinct yet related stem cell programs, according to Whitehead Institute researchers. The differences between these stem cell programs may be significant enough to be exploited by future therapeutics.

Using a mouse model, the lab of Whitehead Institute Founding Member Harvey Lodish, has now determined that combining the cholesterol-lowering drug fenofibrate with glucocorticoids could allow for dramatically lower steroid doses in the treatment of  Diamond Blackfan anemia and other erythropoietin-resistant anemias.

Scientists have applied a new method of analyzing cell states to identify a gene required for breast stem cells to differentiate. This gene, RUNX1, is deregulated or mutated in some leukemias and breast cancers. The novel approach, known as PEACS, could also be used to screen for drugs that activate or inhibit the expression regulators of stem cell differentiation.

The prize honors Jaenisch’s groundbreaking body of work in epigenetics, the development of transgenic animals, and the generation and use of induced pluripotent stem (iPS) cells.

A team of Whitehead Institute scientists has discovered that during division, stem cells distinguish between old and young mitochondria and allocate them disproportionately between daughter cells.

A widely conserved family of RNA-binding proteins known to be expressed in neural stem cells and other stem cell types has now been shown to play a role in controlling both the state and behavior of breast cancer cells.

Induced neural stem cells (iNSCs) hold promise for therapeutic transplantation, but their potential in this capacity has been limited by failed efforts to maintain such cells in their multi-potent NSC state. Now, Whitehead Institute scientists have created iNSCs that remain in the multi-potent state—without ongoing expression of reprogramming factors. This allows the iNSCs to self-renew repeatedly to generate cells in quantities sufficient for therapy.

Scientists have long theorized that the way in which the roughly three meters of DNA in a human cell is packaged to fit within a nuclear space just six microns wide, affects gene expression. Now, Whitehead Institute researchers present the first evidence that DNA structure does indeed have such effects—in this case finding a link between chromosome structure and the expression and repression of key genes.

Induced pluripotent stem cells (iPSCs) may hold the potential to cure damaged nerves, regrow limbs and organs, and perfectly model a patient’s particular disease. Yet these cells can acquire serious genetic and epigenetic abnormalities that lower the cells’ quality and limit their therapeutic usefulness. Now Whitehead Institute researchers have identified a cocktail of reprogramming factors that produces very high quality iPSCs.

Embryonic stem cell (ESC) research has been hampered by the inability to transfer research and tools from mouse ESC studies to their human counterparts, in part because human ESCs are “primed” and slightly less plastic than the mouse cells. Now researchers in the lab of Whitehead Institute Founding Member Rudolf Jaenisch have discovered how to manipulate and maintain human ESCs into a “naïve” or base pluripotent state similar to that of mouse ESCs without the use of any reprogramming factors.