 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Apr 29, 2024 |
| Title |
Novel human cellular model of CDA IV enables comprehensive analysis revealing molecular basis of disease phenotype. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Red blood cell disorders can result in severe anemia. One such disease, congenital dyserythropoietic anemia IV (CDA IV) is caused by heterozygous mutation E325K in the transcription factor KLF1. However, studying the molecular basis of CDA IV is severely impeded by paucity of suitable and adequate quantities of material from anaemic patients and rarity of the disease. We therefore took a novel approach, creating a human cellular disease model system for CDA IV, which accurately recapitulates the disease phenotype. Next, using comparative proteomics we reveal extensive distortion of the proteome and a wide range of disordered biological processes in CDA IV erythroid cells. These include down-regulated pathways governing cell cycle, chromatin separation, DNA repair, cytokinesis, membrane trafficking and global transcription, and upregulated networks governing mitochondria biogenesis. The diversity of such pathways elucidates the spectrum of phenotypic abnormalities that occur with CDA IV and impairment to erythroid cell development and survival, collectively explaining the CDA IV disease phenotype. The data also reveal far more extensive involvement of KLF1 in previously assigned biological processes, along with novel roles in the regulation of intracellular processes not previously attributed to this transcription factor. Overall, the data demonstrate the power of such a model cellular system to unravel the molecular basis of disease and how studying effects of a rare mutation can reveal fundamental biology.
|
| |
|
| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for wildtype and KLF1+/E325K cells.
|
| |
|
| Contributor(s) |
Ferrer-Vicens I, Ferguson DC, Wilson MC, Heesom KJ, Bieker JJ, Frayne J |
| Citation(s) |
37084386 |
| Submission date |
Mar 07, 2023 |
| Last update date |
Apr 29, 2024 |
| Contact name |
Jan Frayne |
| E-mail(s) |
jan.frayne@bristol.ac.uk
|
| Organization name |
University of Bristol
|
| Department |
School of Biochemistry
|
| Street address |
Biomedical Sciences Building, University Walk
|
| City |
Bristol |
| ZIP/Postal code |
BS8 1TD |
| Country |
United Kingdom |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (6)
|
| GSM7083740 |
BEL-A cells, wildtype, day 2 of differentiation 1 |
| GSM7083741 |
BEL-A cells, wildtype, day 2 of differentiation 2 |
| GSM7083742 |
BEL-A cells, wildtype, day 2 of differentiation 3 |
| GSM7083743 |
BEL-A cells, KLF1+/E325K, day 2 of differentiation 1 |
| GSM7083744 |
BEL-A cells, KLF1+/E325K, day 2 of differentiation 2 |
| GSM7083745 |
BEL-A cells, KLF1+/E325K, day 2 of differentiation 3 |
|
| Relations |
| BioProject |
PRJNA941791 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE226782_gene_fpkm_processed.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...