Developmentally-faithful and effective human erythropoiesis in immunodeficient and Kit mutant mice.

Am J Hematol
Authors
Keywords
Abstract

Immunodeficient mouse models have been valuable for studies of human hematopoiesis, but high-fidelity recapitulation of erythropoiesis in most xenograft recipients remains elusive. Recently developed immunodeficient and Kit mutant mice, however, have provided a suitable background to achieve higher-level human erythropoiesis after long-term hematopoietic engraftment. While there has been some characterization of human erythropoiesis in these models, a comprehensive analysis from various human developmental stages has not yet been reported. Here, we have utilized cell surface phenotypes, morphologic analyses, and molecular studies to fully characterize human erythropoiesis from multiple developmental stages in immunodeficient and Kit mutant mouse models following long-term hematopoietic stem and progenitor cell engraftment. We show that human erythropoiesis in such models demonstrates complete maturation and enucleation, as well as developmentally appropriate globin gene expression. These results provide a framework for future studies to utilize this model system for interrogating disorders affecting human erythropoiesis and for developing improved therapeutic approaches.

Year of Publication
2017
Journal
Am J Hematol
Volume
92
Issue
9
Pages
E513-E519
Date Published
2017 Sep
ISSN
1096-8652
DOI
10.1002/ajh.24805
PubMed ID
28568895
PubMed Central ID
PMC5546987
Links
Grant list
R01 DK103794 / DK / NIDDK NIH HHS / United States
R33 HL120791 / HL / NHLBI NIH HHS / United States
T32 HL007574 / HL / NHLBI NIH HHS / United States
U01 HL117720 / HL / NHLBI NIH HHS / United States