Identification of gene co-expression modules associated with long-term engraftment potential hematopoietic stem cells (LT-HSC) by analysis of public transcriptome data.

Abstract

Hematopoietic stem cells with long-term engraftment potential (long-term hematopoietic stem cells - LT-HSC) are the only cells capable of reconstituting the bone marrow, generating all the blood cell lineages, therefore having the major role in a bone marrow transplant context. LT-HSCs are rare cells and, given that the success of a transplant depends on the amount of LT-HSC transplanted, their expansion in vitro has always been a goal in Medicine. However, reproducing conditions that allow these cells to expand to desirable levels without losing their potential remains a challenge. In attempts to optimize the expansion protocols, it is therefore necessary to evaluate both the number of LT-HSCs and their functionality, another important challenge. Although some surface markers of cultured LT-HSC have been recently reported, since they are molecules susceptible to environmental variations, they may lose their validity depending on the cultivation condition, making it necessary to evaluate the maintenance of the functionality of these cells by xenotransplantation assays at each change in the cultivation protocol. Thus, the hypothesis of this work is that through systems biology analysis, it will be possible to identify co-expression modules associated with LT-HSC. Thus, our aim is to use this approach, on public data from fresh LT-HSC populations and heterogeneous populations of cultured hematopoietic cells, to verify whether the expression of core genes from co-expression modules associated with LT-HSC would reflect the relative abundance of these cells in different conditions. To do this, we will analyze publicly available LT-HSC transcriptome data to select a set of core module genes that are shown to be associated with LT-HSC. Our results, in addition to contributing to an understanding of the cell biology of LT-HSCs, may make it possible to devise a strategy for quantifying the enrichment of these cells, which would have important applications in clinical contexts.