Am J Hematol. 2017 Dec 23. doi: 10.1002/ajh.25015. [Epub ahead of print]

Developmental Differences Between Neonatal and Adult Human Erythropoiesis.

Yan H¹, Hale J¹, Jaffray J¹, Li J², Wang Y², Huang Y², An X², Hillyer C¹, Wang N³, Kinet S⁴, Taylor N⁴, Mohandas N¹, Narla A³, Blanc L^5,6.

Abstract

Studies of human erythropoiesis have relied, for the most part, on the in vitro differentiation of hematopoietic stem and progenitor cells (HSPC) from different sources. Here, we report that despite the common core erythroid program that exists between cord blood (CB)- and peripheral blood (PB)-HSPC induced towards erythroid differentiation in vitro, significant functional differences exist. We undertook a comparative analysis of human erythropoiesis using these two different sources of HSPC. Upon in vitro erythroid differentiation, CB-derived cells proliferated 4-fold more than PB-derived cells. However, CB-derived cells exhibited a delayed kinetics of differentiation, resulting in an increased number of progenitors, notably CFU-E. The phenotypes of early erythroid differentiation stages also differed between the two sources with a significantly higher percentage of IL3R^- GPA^- CD34⁺ CD36⁺ cells generated from PB- than CB-HSPCs. This subset was found to generate both BFU-E and CFU-E colonies in colony-forming assays. To further understand the differences between CB- and PB-HSPC, cells at eight stages of erythroid differentiation were sorted from each of the two sources and their transcriptional profiles were compared. We document differences at the CD34, BFU-E, poly- and orthochromatic stages. Genes exhibiting the most significant differences in expression between HSPC sources clustered into cell cycle- and autophagy-related pathways. Altogether, our studies provide a qualitative and quantitative comparative analysis of human erythropoiesis, highlighting the impact of the developmental origin of HSPCs on erythroid differentiation. This article is protected by copyright. All rights reserved.