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
|
Resource |
Human and Animal Cells |
HUDEP-2(RCB4557) |