RRC ID 59725
Author Ludwig LS, Lareau CA, Bao EL, Nandakumar SK, Muus C, Ulirsch JC, Chowdhary K, Buenrostro JD, Mohandas N, An X, Aryee MJ, Regev A, Sankaran VG.
Title Transcriptional States and Chromatin Accessibility Underlying Human Erythropoiesis.
Journal Cell Rep
Abstract 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.
Volume 27(11)
Pages 3228-3240.e7
Published 2019-6-11
DOI 10.1016/j.celrep.2019.05.046
PII S2211-1247(19)30666-7
PMID 31189107
PMC PMC6579117
MeSH Aged Cells, Cultured Chromatin / chemistry Chromatin / metabolism Chromatin Assembly and Disassembly* Erythroid Precursor Cells / cytology Erythroid Precursor Cells / metabolism Erythropoiesis* Female GATA1 Transcription Factor / genetics GATA1 Transcription Factor / metabolism HEK293 Cells Humans Kruppel-Like Transcription Factors / genetics Kruppel-Like Transcription Factors / metabolism Membrane Proteins / genetics Membrane Proteins / metabolism Middle Aged Polymorphism, Single Nucleotide Transcriptome*
IF 7.815
Times Cited 9
Human and Animal Cells HUDEP-2(RCB4557)