Modelling erythropoiesis in congenital dyserythropoietic anaemia type I (CDA-I) for diagnosis and molecular dissection.

Congenital Dyserythropoietic Anaemia type 1 (CDA-I) is an inherited anaemia arising primarily from mutations in C15orf41 and CDAN1, however the molecular mechanisms that cause the disease remain to be fully elucidated. We use an in vitro culture system to study multiple stages of erythropoiesis from CD34+ progenitors of patients with CDA-I. Applying a number of techniques, including ATAC-seq, we show that differentiation of CDA-I patient erythroblasts closely matches that of healthy donors during the early and intermediate stages of erythroid differentiation and maturation. However, a defect in terminal erythropoiesis can be observed in the CDA-I patient derived erythroblasts, resulting in a reduction in the number of enucleated erythroid cells. 32 ATAC-seq samples of cultured erythroblasts from Cogenital DyserythropoieticAnemia Type 1 (CDA-I) CD34 progenitors from 7 Donors, with up to 2 technical replicates for each timepoint during culture (Day7, Day10, Day11, Day13)