Journal
CELL REPORTS
Volume 27, Issue 11, Pages 3228-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2019.05.046
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Funding
- Howard Hughes Medical Institute Medical Research Fellows program
- NIH training grant [T32GM007753]
- Broad Institute Fellows program
- Allen Institute Distinguished Investigator Award
- NIH [R01 DK103794, R33 HL120791, P01 DK32094]
- Howard Hughes Medical Institute
- Klarman Cell Observatory
- New York Stem Cell Foundation (NYSCF)
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Human erythropoiesis serves as a paradigm of physiologic cellular differentiation. This process is also of considerable interest for better understanding anemias and identifying new therapies. Here, we apply deep transcriptomic and accessible chromatin profiling to characterize a faithful ex vivo human erythroid differentiation system from hematopoietic stem and progenitor cells. We reveal stage-specific transcriptional states and chromatin accessibility during various stages of erythropoiesis, including 14,260 differentially expressed genes and 63,659 variably accessible chromatin peaks. Our analysis suggests differentiation stage-predominant roles for specific master regulators, including GATA1 and KLF1. We integrate chromatin profiles with common and rare genetic variants associated with erythroid cell traits and diseases, finding that variants regulating different erythroid phenotypes likely act at variable points during differentiation. In addition, we identify a regulator of terminal erythropoiesis, TMCC2, more broadly illustrating the value of this comprehensive analysis to improve our understanding of erythropoiesis in health and disease.
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