Transcriptome profiling of c-Kit+ hematopoietic stem and progenitor cells enriched from 10-week-old wild-type and Rps19R67?/R67? mutant mice.
This RNA 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 arginine 67 mutation of ribosomal protein Rps19 develops features characteristic of human Diamond-Blackfan anemia, a rare bone marrow failure syndrome. These include 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 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. Using preliminary RNA sequencing study we identify a set of non-canonical components of the p53 signaling pathway which with high likelihood mediate the wide range of pathologies associated with DBA, the experiment if followed up by single cell transcriptome analysis of bone marrow hematopoietic progenitors and RNA sequencing of E14.5 fetal liver from wild-type control and Rps19R67?/R67?, Rps19R67?/R67? Trp53-/- and Trp53-/- mutant embryos.