Helmholtz Gemeinschaft


Transcriptional states and chromatin accessibility underlying human erythropoiesis

PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
[img] Other (Supplemental Material)

Item Type:Article
Title:Transcriptional states and chromatin accessibility underlying human erythropoiesis
Creators Name:Ludwig, L.S. and Lareau, C.A. and Bao, E.L. and Nandakumar, S.K. and Muus, C. and Ulirsch, J.C. and Chowdhary, K. and Buenrostro, J.D. and Mohandas, N. and An, X. and Aryee, M.J. and Regev, A. and Sankaran, V.G.
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.
Keywords:Erythropoiesis, Red Blood Cells, Chromatin Accessibility, Transcriptomics, GWAS, Human Genetics, Hematopoiesis
Source:Cell Reports
Publisher:Cell Press / Elsevier
Page Range:3228-3240
Date:11 June 2019
Official Publication:https://doi.org/10.1016/j.celrep.2019.05.046
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library