The cellular and molecular basis of defects in Down syndrome fetal bone marrow B-lymphopoiesis (DPhil thesis).
ROY A., Roberts I., NERLOV C., Murnane C.
In this project, the identification and characterisation of new progenitor populations in FBM has facilitated existing models of fetal B-lymphopoiesis to be refined. In DS FBM, lymphopoiesis is disrupted with a severe block in B-cell differentiation that appears to occur upstream and is propagated through the newly described progenitors, as well as moderately impaired T-cell development and a skew toward NK lymphopoiesis. These findings were validated at the molecular level, with T21 causing broad changes in both the transcriptome and chromatin accessibility of FBM HSPCs.