Study different scl isoforms in zebrafish primitive and definite hematopoiesis

ZHEN FENG HUA

Publication

Study different scl isoforms in zebrafish primitive and definite hematopoiesis

ZHEN FENG HUA

Abstract

Hematopoiesis is a highly organized program composed of ventral mesoderm induction, hematopoietic stem cell (HSC) specification and subsequent lineage differentiation. The SCL gene, encoding a basic helix-loop-helix (bHLH) transcription factor, has been indicated important for the development of primitive and definitive hematopoiesis. In this research, we reported that zebrafish produces, through an alternative promoter, a novel truncated scl isoform, scl-b, which manifests a distinct spatiotemporal expression pattern from the previous reported full-length scl-a. Functional analysis reveals that scl-a and scl-b is redundant for the initiation of primitive hematopoiesis. However, they play different roles in primitive erythrocyte differentiation. In addition, the specification of definitive HSCs specifically requires scl-b but not scl-a. Furthermore, we provide evidence suggesting that the functional differences of scl-a and scl-b likely result from their different protein expression levels, possibly coming from their different protein stabilities. Taken together, our findings suggest that hematopoietic cells at different stage of hematopoietic hierarchy are properly governed by a gradient of Scl proteins established through the distinct spatial and temporal expression of these two different scl isoforms.