For the first time, a comprehensive catalogue has been generated of transcription factors and other proteins that regulate the sophisticated processes leading to the formation of different types of blood cells, including the white ones by blood stem cells, the scientific paper Science reports.

This study is one of three BLUEPRINT papers published in Science. The BLUEPRINT project aims at deciphering the epigenomes of more than 100 different types of blood cells. It is one of the two first so-called European high impact research initiatives.

Understanding the molecular basis of cell differentiation is essential for the advancement of transplantation and regenerative medicine, the authors, spearheaded from RadboudUniversity, Cambridge Universities,and the Welcome Trust Sanger Institute say. The Science study by Chen et all highlights the complexity of the regulation of fating events (cell formation and growth) that determine the states of closely related populations of blood progenitor cells.

RNA processing

To manufacture a protein, cells need to transcribe the DNA in the nucleus into a messenger called RNA. The spectrum of RNA molecules carries the instruction for cells how to produce proteins. BLUEPRINT researchers discovered the extent by which the RNA is cut and pasted together in different ways during the various fating events, leading to specific constellations of proteins for each of these stages.

"We have identified thousands of novel places where the RNA is processed in an alternative way" said Willem H Ouwehand, Professor of Experimental Haematology at the University of Cambridge and the Wellcome Trust Sanger Institute.

"This new and freely available catalogue of RNA molecules in blood progenitor cells provides a rich resource for researchers worldwide", commented Dr Nicole Soranzo from the Wellcome Trust Sanger Institute in Cambridge. It will be of great value in studies which aim to manipulate blood stem cells and their progeny and is important for future developments in stem cell transplantation therapy, as well as efforts in regenerative medicine

BLUEPRINT: Epigenetics of blood

After the human genome was deciphered, it became apparent that knowing the DNA code and how it is organised in chromosomes is insufficient to understand how the code is used to determine the identity of cells. There are lots of different types of cells in the body and each cell has the same DNA content, yet cells differ greatly in their appearance and function. They change in response to outside signals and as a consequence of aging and their altered states underlie diseases. Thus, the way the genetic information is used differs between each type of cell and this difference is in part determined by how DNA is packaged in chromosomes. Epigenetics aims at unravelling this packaging through structural adaptation of chromosomes which determines how DNA elements are regulated. The newly gained layers of information, which are unique to a particular type of cells are placed on "top of the genome" to form a master plan or blueprint of the cell.