Genetic code expansion in human stem cells

Researchers report the generation of human stem cells whose genetic code incorporates noncanonical amino acids (ncAAs). ncAAs can be genetically incorporated into proteins for studying and manipulating protein structure and function. Several ncAAs have been successfully incorporated into bacteria, yeast, mammalian cells, and other multicellular organisms but not human systems. Peter Schultz and colleagues incorporated ncAAs into human hematopoietic stem cells (HSCs), which are precursors of blood cells, using a vector derived from Epstein-Barr virus that is capable of self-replication. The viral vector encoded a transfer RNA capable of incorporating a variety of lysine-derived ncAAs into proteins at the UAG stop codon, along with the corresponding aminoacyl-tRNA synthetase enzyme. The authors introduced this vector into human HSCs isolated from umbilical cord blood and found that both the initial HSCs and their differentiated progeny incorporated ncAAs into proteins encoded by the vector. The modified HSCs could be engrafted into mice, resulting in the production of ncAA-containing proteins when the mice were supplied with dietary ncAAs. The results suggest that other human stem cell types could be similarly modified to use ncAAs, providing tools to study human proteins in cell culture and living organisms, according to the authors.

###

Article #19-14408: “Expanding the genetic code of the human hematopoietic system,” by Sida Shao, Minseob Koh, and Peter G. Schultz.

MEDIA CONTACT: Peter G. Schultz, Scripps Research Institute, La Jolla, CA; tel: 858-784-9300; e-mail:

[email protected]