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Direct Lineage Reprogramming of Adult Mouse Fibroblast to Erythroid Progenitors
Published on: December 14, 2018
Ontogeny of erythroid gene expression.
Paul D Kingsley1, Emily Greenfest-Allen, Jenna M Frame
1Department of Pediatrics, University of Rochester Medical Center, Center for Pediatric Biomedical Research, Rochester, NY 14642, USA.
Blood
|December 18, 2012
Summary
Primitive and definitive erythroid cells show distinct gene expression patterns, particularly in aquaporin usage and reactive oxygen species accumulation. Most gene complexity in erythroid precursors is established by the proerythroblast stage.
Area of Science:
- Hematology
- Molecular Biology
- Genomics
Background:
- Erythroid ontogeny involves primitive and definitive lineages with shared morphology but differing cell size and globin expression.
- Understanding lineage-specific gene expression is crucial for deciphering erythropoiesis.
Purpose of the Study:
- To compare global gene expression in primitive, fetal definitive, and adult definitive erythroid cells.
- To identify lineage-restricted gene expression and functional differences during erythroid maturation.
Main Methods:
- Purification of erythroid cells from embryonic, fetal, and adult mice at equivalent maturation stages.
- Global gene expression profiling using transcriptomics.
- Bioinformatic analysis of gene expression data.
Main Results:
- Most transcriptional complexity in erythroid precursors is present by the proerythroblast stage.
- Primitive and definitive erythroid lineages share many non-housekeeping genes, but exhibit alternate gene usage within functional categories.
- Selective expression of aquaporins (e.g., AQP3/8 in primitive, AQP1/9 in adult definitive) and differential reactive oxygen species accumulation were observed.
Conclusions:
- Erythroid lineage specification involves significant, albeit overlapping, transcriptional programs.
- Distinct functional pathways, such as reactive oxygen species transport via aquaporins, differentiate primitive and definitive erythroid cells.
- A comprehensive database (ErythronDB) was created to share these global expression data.
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