Identification of protein co-expression modules associated with hematopoietic stem cells of long-term engraftment potential (LT-HSC) in fresh populations.

• Grant number: 23/17841-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2024
• End date: February 28, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Karina Griesi Oliveira
• Grantee: João Pedro Pereira Poit
• 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

In view of the functional importance of hematopoietic stem cells with long-term engraftment potential (LT-HSC) for bone marrow reconstitution, whether in the context of allogeneic or autologous transplants (such as in recent gene therapy applications), and their low frequency among hematopoietic cells, there are still many efforts to optimize conditions for manipulation and ex vivo expansion of this cell population. The validity of surface markers for enriching LT-HSC cultivated under different conditions is still uncertain, and therefore, demonstrating the presence of these cells still needs to be done through xenotransplantation in mice with each new attempt to optimize the protocol, a laborious and time-consuming strategy. Thus, the development of tools for the prospective evaluation of the abundance of LT-HSC cultivated by potentially more robust strategies, compared to the use of cell surface markers, and simpler execution is extremely important as it can facilitate tests to optimize HSC culture conditions aiming at maintaining their potential. In this sense, it is crucial to understand in depth which gene groups act together to determine this cellular phenotype. Analyzing this question at the proteomic level and with a systemic analysis approach is a unique contribution to the literature that can provide a deeper understanding of which genes could represent the ideal markers for this cell population.