PUBLICATION
Cohesin rad21 mutation dysregulates erythropoiesis and granulopoiesis output within the whole kidney marrow of adult zebrafish
- Authors
- Gimenez, G., Kalev-Zylinska, M.L., Morison, I., Bohlander, S.K., Horsfield, J.A., Antony, J.
- ID
- ZDB-PUB-241117-7
- Date
- 2024
- Source
- American journal of physiology. Cell physiology 328(1): C9-C19 (Journal)
- Registered Authors
- Antony, Jisha, Horsfield, Jules
- Keywords
- RAD21, cohesin, hematopoiesis, leukemia, myeloid dysplastic syndrome
- Datasets
- GEO:GSE275537, GEO:GSE275536
- MeSH Terms
-
- Erythropoiesis*/genetics
- Animals
- Chromosomal Proteins, Non-Histone/genetics
- Chromosomal Proteins, Non-Histone/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Zebrafish*/genetics
- Kidney/metabolism
- Kidney/pathology
- Cohesins
- Mutation
- Cell Differentiation/genetics
- Cell Cycle Proteins*/genetics
- Cell Cycle Proteins*/metabolism
- Granulocytes*/metabolism
- Granulocytes*/pathology
- Bone Marrow/metabolism
- Bone Marrow/pathology
- PubMed
- 39548947 Full text @ Am. J. Physiol. Cell Physiol.
Citation
Gimenez, G., Kalev-Zylinska, M.L., Morison, I., Bohlander, S.K., Horsfield, J.A., Antony, J. (2024) Cohesin rad21 mutation dysregulates erythropoiesis and granulopoiesis output within the whole kidney marrow of adult zebrafish. American journal of physiology. Cell physiology. 328(1):C9-C19.
Abstract
Cohesin complex is essential for cell division and for regulating cell type-specific gene expression programs. Mutations in genes encoding the cohesin subunits are associated with hematological malignancies, pre-leukemia and clonal hematopoiesis of indeterminate potential. In this study, we examined how cohesin mutation impacts hematopoiesis using adult zebrafish that carry heterozygous germline nonsense mutation in the cohesin subunit, rad21 (rad21+/-) that is orthologous to human RAD21. Single cell RNA sequencing analyses showed that adult zebrafish harboring rad21+/- mutation exhibit significant transcriptional dysregulation within the whole kidney marrow and have altered erythroid and granulocyte output. Erythroid progenitors were expanded in rad21+/- and erythroid differentiation was altered. The expression profile of several erythroid genes, including gata1a, was dysregulated in rad21+/- erythroid cells. Mature granulocyte population declined in rad21+/-, and the transcriptional program of granulocytes was impaired but granulocytic maturation was maintained. Granulocytes from rad21+/- showed upregulation of stress hematopoiesis factor, cebpb. These findings show that normal rad21 is required to maintain steady erythropoiesis and granulopoiesis in the adult zebrafish marrow.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping