PUBLICATION
tfec controls the hematopoietic stem cell vascular niche during zebrafish embryogenesis
- Authors
- Mahony, C.B., Fish, R.J., Pasche, C., Bertrand, J.Y.
- ID
- ZDB-PUB-160713-4
- Date
- 2016
- Source
- Blood 128(10): 1336-45 (Journal)
- Registered Authors
- Bertrand, Julien, Mahony, Christopher, Pasche, Corentin
- Keywords
- none
- MeSH Terms
-
- Hematopoiesis/physiology
- Gene Expression Regulation, Developmental
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism
- Animals
- Embryo, Nonmammalian/cytology*
- Embryo, Nonmammalian/metabolism
- Cytokines/genetics
- Cytokines/metabolism
- Embryonic Development/physiology*
- Stem Cell Niche/physiology*
- Animals, Genetically Modified/embryology*
- Animals, Genetically Modified/genetics
- Animals, Genetically Modified/metabolism
- Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics
- Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism*
- Hematopoietic Stem Cells/cytology*
- Hematopoietic Stem Cells/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 27402973 Full text @ Blood
Citation
Mahony, C.B., Fish, R.J., Pasche, C., Bertrand, J.Y. (2016) tfec controls the hematopoietic stem cell vascular niche during zebrafish embryogenesis. Blood. 128(10):1336-45.
Abstract
In mammals, embryonic hematopoiesis occurs in successive waves, culminating with the emergence of hematopoietic stem cells (HSCs) in the aorta. HSCs first migrate to the fetal liver (FL) where they expand, before they seed the bone marrow niche, where they will sustain hematopoiesis throughout adulthood. In zebrafish, HSCs emerge from the dorsal aorta, and colonize the caudal hematopoietic tissue (CHT). Recent studies showed that they interact with endothelial cells (ECs), where they expand, before they reach their ultimate niche, the kidney marrow. We identified tfec, a transcription factor from the mitf family, which is highly enriched in caudal endothelial cells (cECs) at the time of HSC colonization in the CHT. Gain-of-function assays indicate that tfec is capable of expanding HSC-derived hematopoiesis, in a non cell-autonomous fashion. Furthermore, tfec mutants (generated by CRISPR/Cas9) showed reduced hematopoiesis in the CHT, leading to anemia. Tfec mediates these changes by increasing the expression of several cytokines in cECs from the CHT niche. Among these, we found kitlgb, which could rescue the loss of HSCs observed in tfec mutants. We conclude that tfec plays an important role in the niche to expand hematopoietic progenitors through the modulation of several cytokines. The full comprehension of the mechanisms induced by tfec will represent an important milestone towards the expansion of HSCs for regenerative purposes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping