title: tfec controls the hematopoietic stem cell vascular niche during zebrafish embryogenesis.
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 toward the expansion of HSCs for regenerative purposes.
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, and.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Mahony
authors.affiliation: Department of Genetic and Development, Faculty of Medicine, Centre Medical Universitaire, University of Geneva, Geneva, Switzerland.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Fish
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, and.
authors.forename: Corentin
authors.initials: C
authors.lastname: Pasche
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, and.
authors.forename: Julien Y
authors.initials: JY
authors.lastname: Bertrand
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000378:metabolism; D047108:Embryonic Development / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D055153:Stem Cell Niche / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D016207:Cytokines; C570685:Tfec protein, zebrafish; D029961:Zebrafish Proteins