ANALYSIS OF SIGNAL NETWORKS IN HEMATOPOIETIC STEM CELLS DETERMINING THE STEM CELL FATE

Swati Sharma, Gurudutta U. Gangenahalli* and Upma Singh

ABSTRACT

Hematopoietic stem cells (HSCs) are the unique cells having the core property of self-renewal/ proliferation and differentiation which make them capable of giving rise to all blood cell lineages. Proliferation and migration of HSCs in a regulated manner maintain healthy homeostasis by the interplay between differentiation, self-renewal/ proliferation and dormancy. Here, we identified and described functional molecular signatures eliciting different biochemical responses in molecular signaling of CD34+ HSCs in response to a cocktail of Interleukin-3 (IL-3), Fms-Like Tyrosine Kinase-3 Ligand (FLT-3), and Stem Cell Factor (SCF), using a network-based approach. The bioinformatic analysis of sum total of 22,283 gene transcripts (extracted from microarray data GSE3003) resulted into the characterization of genes (in two subgroups: up-regulated & down-regulated) eliciting stem cell responses: proliferation, differentiation and self-renewal. As in-vitro proof of concept, nine significant genes, RBM3, DHX32, PSMD9, SAR1A, SMYD3, ST6GAL1, CKAP4, CTR9 are selected for further analysis, having a key role in molecular signaling. Taken together, our results showed the identification of some novel regulatory genes through computational means and their functional importance in biological pathways.

Keywords: Hematopoietic stem cells (HSCs), self-renewal, proliferation.