Genome-Scale Technology Driven Advances to Research into Normal and Malignant Haematopoiesis

Berthold Göttgens

doi:10.6064/2012/437956

Abstract

Haematopoiesis or blood development has long served as a model system for adult stem cell biology. Moreover, when combined, the various cancers of the blood represent one of the commonest human malignancies. Large numbers of researchers have therefore dedicated their scientific careers to studying haematopoiesis for more than a century. Throughout this period, many new technologies have first been applied towards the study of blood cells, and the research fields of normal and malignant haematopoiesis have also been some of the earliest adopters of genome-scale technologies. This has resulted in significant new insights with implications ranging from basic biological mechanisms to patient diagnosis and prognosis and also produced lessons likely to be relevant for many other areas of biomedical research. This paper discusses the current state of play for a range of genome-scale applications within haemopoiesis research, including gene expression profiling, ChIP-sequencing, genomewide association analysis, and cancer genome sequencing. A concluding outlook section explores likely future areas of progress as well as potential technological and educational bottlenecks.

Highlights

Haematopoiesis represents the process whereby multipotential blood stem and progenitor cells differentiate into more than 10 distinct mature blood cell types
Long-term formation of mature blood cells from blood stem cells forms the basis of successful bone marrow transplantation, which represents one of the most widely used stem cell treatments currently in use
It allows for the detection of the presence of blood stem cells in complex mixtures of cells, with the most advanced protocols allowing for the transplantation of a single blood stem cell to give rise to long-term donor-derived haematopoiesis in the transplant recipient [6]

Summary

Introduction

Haematopoiesis represents the process whereby multipotential blood stem and progenitor cells differentiate into more than 10 distinct mature blood cell types. Following the advent of high-throughput sequencing technologies, it was quickly realised that genomewide analysis of histone modi cation status is amenable to this new technology To this end, the sheared chromatin fragments are subjected to sequencing following immunoprecipitation with suitable antibodies (chromatin immunoprecipitation or ChIP), with the whole technique commonly referred to as ChIP-Seq. Posttranslational modi cations indicating both active and repressed transcriptional status are well recognized and have been mapped at genome scale in a variety of both mouse and human blood cell types [71,72,73,74,75,76,77,78,79,80]. Concerted research efforts are currently directed at generating genomewide maps of both the locations of 5hmC as well as the binding sites of Tet proteins [96, 97, 104,105,106,107,108,109,110]

Genome-Scale Transcription Factor Maps

Genomewide Association Studies

Cancer Genome Sequencing