Single cell transcriptomic analysis of bone marrow hematopoietic stem and progenitors cells isolated from 10-week-old wild-type control, Rps19R67?/R67?, Rps19R67?/R67? Trp53-/- and Trp53-/- mutant mice.
This single cell transcriptome sequencing experiment is part of the study \"Preclinical animal model of Diamond-Blackfan anemia with single amino acid mutation of ribosomal protein Rps19\".  A mouse model with this mutation develops features characteristic of human Diamond-Blackfan anemia, a rare bone marrow failure syndrome, including hematologic dysfunctions, early onset growth delay, intrinsic anemia, severe craniofacial, skeletal, urogenital, cardiovascular, and cerebral abnormalities leading to premature lethality during the adolescence of the mouse. This DBA mouse model exhibits cell intrinsic activation of the Trp53 signaling pathway in hematopoietic stem cells (HSCs) leading to reduced erythroid lineage development that may be rescued after inactivation of the tumor suppressor Trp53. The study uncovers that the development of the DBA phenotype significantly involves non-canonical components of the p53 signaling pathway in the etiopathogenesis of DBA with the Rps19R67? mutation leading to the disrupted hematopoietic hierarchy starting at the stage of short-term repopulating stem cells and the central role of induced Trp53 expression and upregulation of its non-canonical targets in the mediation of neural crest lineage deficiency-mediated development of craniofacial malformations in this model.