GIS Scientists Propose A New Paradigm For Embryonic Stem Cells, Potentially Speeding Up Development Of Disease Therapies

Scientists from the Genome Institute of Singapore (GIS) have put forward a novel explanation for the pluripotency[1] of embryonic stem (ES) cells. Their groundbreaking explanation opens new doors for understanding how stem cells create specific cell types, fundamental knowledge that will drive changes and improvements in the therapeutic and translational usage of stem cells. A better understanding of ES cells could help advance the development of treatments for diseases such as diabetes, Parkinson's disease, and Huntington's disease. The work, published in the journal Cell Stem Cell, was led by Dr Bing Lim, Senior Group Leader of the Stem Cell and Developmental Biology department at the GIS, and Kyle Loh, GIS student from Dr Lim's lab.

By re-examining current data with a fresh eye, Lim and Loh were able to suggest a novel paradigm that may resolve the 30-year-old mystery behind pluripotency. The prevailing model of stem cell pluripotency suggests that stem cell genes active in ES cells prevent these stem cells from turning into specific cell types. This model accounts for how ES cells can remain undifferentiated, but is unable to explain convincingly the ability of stem cells to create any bodily cell type. Lim and Loh suggest that, contrary to current thinking, individual stem cell genes do not completely suppress differentiation, but instead actively direct ES cells to produce particular bodily cell types. In their new paradigm, Lim and Loh propose that the activation of a combination of such stem cell genes within ES cells is what enables ES cells to create any bodily cell type.

[1] Pluripotency refers to the ability of ES cells to differentiate into all bodily cell types. ES cells can potentially create, on demand, any cell type that clinicians or scientists need for therapeutic, biotechnological, or research purposes. Hence, the cells are currently used as a source of specialized cell types used in cell replacement therapies. An understanding of how ES cells are able to produce all these cell types is of intense pragmatic and theoretical interest.

Source
Genome Institute of Singapore

Enzyme Essential For Healthy Lung Development Discovered

Investigators at The Saban Research Institute of Children's Hospital Los Angeles have provided the first evidence that Eya1 protein phosphatase is a crucial regulator of the development of embryonic lung epithelial stem cells.

The correct functioning of lung epithelium is essential to life. Cellular polarity of lung epithelial cells, meaning that they have an asymmetrical orientation or a front and back, is crucial. Dysregulation of cell polarity has been associated with developmental disorders as well as cancer. Until now, little has been known about the mechanism that controls cell polarity, cell fate and self-renewal of embryonic lung epithelial stem cells. David Warburton, MD, director of Developmental Biology and Regenerative Medicine at The Saban Research Institute, and Ahmed El-Hashash, PhD, senior research scientist carrying out this study, will release their findings in the upcoming issue of Development.

"We know that loss of polarity in pulmonary epithelial cells is associated with lung cancer and chronic obstructive pulmonary disease. Knowing that Eya1 regulates polarity, we now have another target for intervening in those disease processes," said Dr. Warburton.

They have determined that Eya1, a protein phosphatase, controls cell polarity, cell fate and self-renewal in the mouse embryonic lung epithelial stem cells. They have also provided the first evidence that these stem cells are polarized with characteristic perpendicular cell divisions.

In vivo and in vitro experiments showed that interfering with Eya1 phosphatase function resulted in defective epithelial cell polarity and mitotic spindle orientation; disrupted Numb, a cell fate determinant; and inactivated Notch signaling, which is involved in cell segregation and division, thereby establishing Eya1 as an important regulator in the development of embryonic lung stem cells.

"Identification of Eya1 mechanisms of regulating cell polarity, cell fate and self-renewal, will help to harness the regenerative potential of lung stem cells, and to identify novel targets for the prevention or rescue therapy of fatal lung disease, and for lung regeneration. This will also help to develop stem cell-based therapy to treat patients with lung diseases, " said Dr. El-Hashash, PhD. "Solutions to the problems concerning regeneration of lung tissue for restoration of functional alveoli are at the cutting edge of identifying novel therapeutic options for lung diseases like COPD and fibrosis."

Source:
Ellin Kavanagh
Children's Hospital Los Angeles