Son is necessary for proper vertebrate blood development.

Rebecca L Belmonte,David L Stachura,Isabella L Engbretson,Eun-Young Erin Ahn,Jung-Hyun Kim,Illiana Cajias,Daniel R Larson

doi:10.1371/journal.pone.0247489

Abstract

The gene SON is on human chromosome 21 (21q22.11) and is thought to be associated with hematopoietic disorders that accompany Down syndrome. Additionally, SON is an RNA splicing factor that plays a role in the transcription of leukemia-associated genes. Previously, we showed that mutations in SON cause malformations in human and zebrafish spines and brains during early embryonic development. To examine the role of SON in normal hematopoiesis, we reduced expression of the zebrafish homolog of SON in zebrafish at the single-cell developmental stage with specific morpholinos. In addition to the brain and spinal malformations we also observed abnormal blood cell levels upon son knockdown. We then investigated how blood production was altered when levels of son were reduced. Decreased levels of son resulted in lower amounts of red blood cells when visualized with lcr:GFP transgenic fish. There were also reduced thrombocytes seen with cd41:GFP fish, and myeloid cells when mpx:GFP fish were examined. We also observed a significant decrease in the quantity of T cells, visualized with lck:GFP fish. However, when we examined their hematopoietic stem and progenitor cells (HSPCs), we saw no difference in colony-forming capability. These studies indicate that son is essential for the proper differentiation of the innate and adaptive immune system, and further investigation determining the molecular pathways involved during blood development should elucidate important information about vertebrate HSPC generation, proliferation, and differentiation.

Highlights

Blood development is the process by which blood cells acquire specific characteristics through carefully regulated gene expression [1]
Quantitation of these data can be seen in S3D Fig. Quantitative reverse transcriptase PCR (qRT-PCR) showed a significant decrease in the expression of band3 and hbaa1, both specific markers of mature erythrocytes, when son MO was injected compared to control embryos (Fig 1F)
We report that son is necessary for proper blood formation through an analysis of mature blood cells and embryonic hematopoietic stem and progenitor cells (HSPCs)

Summary

Introduction

Blood development (hematopoiesis) is the process by which blood cells acquire specific characteristics through carefully regulated gene expression [1]. All blood cells arise from hematopoietic stem cells (HSCs), which are adult stem cells capable of self-renewal and differentiation into more developmentally restricted blood progenitor cells [2,3,4]. HSCs differentiate into either a common myeloid progenitor (CMP) or a common lymphoid progenitor (CLP). Biotechnology (CSUPERB) (New Investigator Awards to D.L.S.), NSF MRI (proposal 1626406), a California State University Chico Internal Research Grant (to D.L.S.), Student Research and Creativity Awards from California State University, Chico (to R.B.) and the NIH (R01CA190688 to E.-Y.E.A. and R15DK114732-01 to D.L.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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Conclusion