This project aims to resolve the molecular mechanisms that drive normal blood cell development to achieve activation of lineage specific programs as well as lineage restriction. The analysis will be based on our single cell RNA/ATAC seq data providing a high resolution map of lymphocyte development in the BM. By the development of novel high throughput sequencing methods for resolution of gene regulatory networks we intend to understand the driving forces of lymphocyte development. Our analysis will also open for novel possibilities to explore the underlying causes of malignant transformation of blood cells in leukemia. One of the most prominent features of the leukemia cells is a block in differentiation preventing normal progression in the developmental trajectory. We hypothesize that this may be a consequence of transformation induced creation of new basins of attraction where the leukemic cells find stable residence outside of the control of normal mechanisms for homeostasis. By imposing SC data from leukemic cells to the normal differentiation trajectory, we intend to identify molecular discrepancies underlying the observed developmental block.