A new type of pluripotent stem cell has been discovered by scientists at the Salk Institute. The cells’ identity is linked to their location in a developing embryo. The stem cells usually used in scientific study have an identity linked to their time-related stage of development.
Pluripotent stem cell are cells capable of developing into any type of tissue.
The Salk scientists have used these new stem cells for developing the first robust method of integrating human stem cells into nonviable mouse embryos. This was done in a laboratory dish such that the human cells started to differentiate into early-stage tissues.
Senior author Professor Juan Carlos Izpisua Belmonte, who holds Salk’s Roger Guillemin Chair, said:
“The region-specific cells we found could provide tremendous advantages in the laboratory to study development, evolution and disease, and may offer avenues for generating novel therapies."
Region-selective Pluripotent Stem Cells
The researchers have named this new form of cells “region-selective pluripotent stem cells,” or rsPSCs for short.
The rsPSCs were simpler to grow in the laboratory than traditional human pluripotent stem cells. They also offer advantages for large-scale production and gene editing, both sought after features for cell replacement therapies.
In order to produce the cells, the Salk team devised a combination of chemical signals which directed human stem cells in a lab dish to become spatially oriented.
The spatially oriented human stem cells (human rsPSCs) were then inserted into certain regions of partially dissected mouse embryos and cultured them in a dish for 36 hours.
Concurrently, they also inserted human stem cells cultured using conventional methods, so that they could compare existing techniques to their new technique.
According to first author Jun Wu, a postdoctoral researcher in Izpisua Belmonte’s lab:
“The region selective-state of these stem cells is entirely novel for laboratory-cultured stem cells and offers important insight into how human stem cells might be differentiated into derivatives that give rise to a wide range of tissues and organs. Not only do we need to consider the timing, but also the spatial characteristics of the stem cells. Understanding both aspects of a stem cell’s identity could be crucial to generate functional and mature cell types for regenerative medicine."
Juan Carlos Izpisua Belmonte et al. An alternative pluripotent state confers interspecies chimaeric competency. Nature, 2015; DOI: 10.1038/nature14413
Brons, I. G. M. et al. Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448, 191–195 (2007)
Kojima, Y. et al. The transcriptional and functional properties of mouse epiblast stem cells resemble the anterior primitive streak. Cell Stem Cell 14, 107–120 (2014)
Photo: a novel type of human stem cell is shown in green integrating and developing into the surrounding cells of a nonviable mouse embryo. Red indicates cells of endoderm lineage. Endoderm cells can give rise to tissue that covers organs from the digestive and respiratory systems. The new stem cell, developed at the Salk Institute, holds promise for one day growing replacement functional cells and tissues. Credit: Salk Institute