Ontogenetically distinct neutrophils differ in function and transcriptional profile in zebrafish

Area of Science:

• Immunology
• Developmental Biology
• Zebrafish Hematopoiesis

Background:

• Leukocytes are traditionally viewed as having distinct origins and non-overlapping functions.
• Limited knowledge exists regarding the specific functions and phenotypes of ontogenetically distinct neutrophil populations.

Purpose of the Study:

• To investigate the functional and phenotypic differences between neutrophil populations derived from distinct developmental origins in zebrafish.
• To compare the migratory properties and transcriptional profiles of rostral and caudal neutrophils at steady state and during injury response.

Main Methods:

• Utilized a photoconvertible transgenic zebrafish line (Tg(mpx:Dendra2)) for in vivo labeling of neutrophils.
• Compared migratory capacities and performed single-cell expression profiling of distinct neutrophil populations.
• Analyzed neutrophil behavior and transcriptional profiles during steady state and following injury.

Main Results:

• Rostral neutrophils demonstrated higher csf3b expression and superior migration capacity compared to caudal neutrophils at steady state.
• Upon injury, both neutrophil populations exhibited shared core transcriptional profiles alongside subset-specific signatures.
• Both rostral and caudal neutrophils were recruited to injury sites, with caudal neutrophils showing heterogeneous responses.

Conclusions:

• Co-existing neutrophil populations originating from distinct developmental sources display significant functional differences.
• Understanding these distinct neutrophil behaviors is crucial for comprehending immune responses and hematopoiesis.
• The study highlights ontogeny as a key determinant of neutrophil function and response heterogeneity.