Hematopoiesis is the continuous process by which new blood cells are formed. Hematopoietic Stem Cells (HSCs) sit at the apex of hematopoiesis and have the ability to differentiate into all mature blood lineages. HSCs accumulate mutations with age. Most of these mutations do not affect fitness, hence selection does not act upon them. However, certain mutations in HSCs confer a fitness advantage and lead to clonal expansions of these mutant blood cells, in a process that is termed as clonal hematopoiesis(CH)[1]. CH has been shown to be a precursor state for hematologic cancers, and also influence pathogenesis of age related cardiovascular diseases(CVD). The vast majority of the mutations in CH occur mainly in two genes DNMT3A, and TET2 both of which are involved in epigenetic regulation[2-3]. However, we lack a clear understanding of how these mutations impact hematopoiesis differentiation topology and the mechanisms underlying pathogenesis in CVD. To better understand the mechanisms underlying CH, we aim to investigate alterations in gene regulatory networks in CH using scRNAseq data from mice and humans. Towards that end, we have developed computational workflows for analysis of scRNAseq data and building of gene regulatory networks. Systematic analysis of large scale scRNAseq data is compute intensive. This project will identify gene regulatory mechanisms implicated CH which will increase our understanding of how CH mutations influence disease pathogenesis. References : 1) Siddhartha Jaiswal, Benjamin L. Ebert ,Clonal hematopoiesis in human aging and disease.Science366,eaan4673(2019).DOI:10.1126/science.aan4673 2) T. McKerrell et al., Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hematopoiesis. Cell Reports 10, 1239–1245 (2015). doi: 10.1016/j. celrep.2015.02.005; pmid: 25732814 3) R. Acuna-Hidalgo et al., Ultra-sensitive Sequencing Identifies High Prevalence of Clonal Hematopoiesis-Associated Mutations throughout Adult Life. Am. J. Hum. Genet. 101,50–64 (2017). doi: 10.1016/j.ajhg.2017.05.013; pmid: 28669404