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| Status |
Public on Apr 04, 2017 |
| Title |
In vitro expansion of normal and Diamond Blackfan anemia-derived peripheral blood erythroid progenitors |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The Affymetrix Human Gene 2.0 ST array was used to measure differential expression of RNA isolated from normal and Diamond Blackfan anemia (DBA) erythroid progenitors after ex vivo expansion of circulating, peripheral blood derived hematopoietic stem cells under erythroid growth conditions. The gene-level probe summaries reported in this series were computed using RMA as implemented in the Bioconductor package Oligo v1.36.1.
Diamond Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by erythroid aplasia, usually without perturbation of other hematopoietic lineages. Approximately 65% of DBA patients with autosomal dominant inheritance have heterozygous mutations or deletions in ribosomal protein (RP) genes while <1% of patients with X-linked inheritance have been identified with mutations in the transcription factor, GATA1. Erythroid cells from patients with DBA have not been well characterized and the mechanisms underlying the erythroid specific effects of either RP or GATA1 associated DBA remain unclear. We have developed an in vitro culture system to expand peripheral blood CD34+ progenitor cells from patients with DBA and differentiate them into erythroid cells. Cells from patients with RP or GATA1 mutations showed decreased proliferation and delayed erythroid differentiation compared to controls. RNA transcript analyses of erythroid cells from controls and patients with RP or GATA1 mutations showed distinctive differences, with upregulation of heme biosynthesis genes prominently in RP-mediated DBA and failure to upregulate components of the translational apparatus in GATA1-mediated DBA. Our data show that dysregulation of translational function is a common feature of DBA caused by both RP and GATA1 mutations.
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| Overall design |
37 samples analyzed including 10 normal CD44+/CD235+, 8 normal CD44+/235-, 5 DBA CD44+/235+, and 14 DBA CD44+/CD235- samples.
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| Contributor(s) |
Farrar JE, Bodine DM |
| Citation(s) |
28377399 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 HL079571 |
A Vital tool for the Study of DBA: The Diamond Blackfan Anemia Registry |
FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH |
Jeffrey M Lipton |
| K08 HL092224 |
Functional Analysis of RPL35A Alterations in Diamond Blackfan Anemia |
UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES |
Jason Eli Farrar |
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| |
| Submission date |
Nov 04, 2016 |
| Last update date |
Mar 15, 2019 |
| Contact name |
Jason Eli Farrar |
| E-mail(s) |
jefarrar@uams.edu
|
| Phone |
501-603-1224
|
| Organization name |
University of Arkansas for Medical Sciences
|
| Department |
Pediatrics/Hematology-Oncology
|
| Street address |
1 Children's Way, #512-10
|
| City |
Little Rock |
| State/province |
AR |
| ZIP/Postal code |
72202 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL16686 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (37)
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| Relations |
| BioProject |
PRJNA352491 |
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