Identification of co-expression modules associated with enrichment of long-term hematopoietic stem cells (LT-HSC) at the transcriptional and protein levels

• Grant number: 23/17638-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: February 01, 2024
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Karina Griesi Oliveira
• Grantee: Victoria de Paiva Oliveira
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil
• Associated research grant: 22/03118-1 - Identification of hematopoietic stem cells gene expression signature using systems biology and machine learning approaches, AP.PNGP.PI

Abstract

Hematopoietic stem cells with long-term engraftment potential (long-termhematopoietic stem cells - LT-HSC) are the only cells capable of reconstituting the bonemarrow, generating all cell lineages that make up the blood, therefore having a large relevancein a bone marrow transplant context. LT-HSC are rare cells and, given that the success of atransplant depends on the quantity of this type transplanted, their in vitro expansion hasalways been a medical objective. However, it has not yet been possible to reproduceconditions that allow the expansion of these cells to desirable levels without losing theirpotential. When optimizing expansion protocols, it is necessary, in the end, to evaluate boththe number of LT-HSC and their functionality, another important challenge. Although somesurface markers of cultured LT-HSC have been recently reported, these may lose their validitydepending on the cultivation condition as they are molecules susceptible to environmentalvariations, making it necessary to evaluate the maintenance of the functionality of these cellsby xenotransplantation assays at each change in the cultivation protocol. Thus, this project aims the objective of generation of transcriptome and proteome data for LTHSC from fresh and in-house cultured cells and, through correlation with the analysis of publicly available LT-HSC transcriptome data, and then select a set of core genes from LTHSC modules expression that are associated with LT-HSC.