Domain-focused CRISPR screen identifies HRI as a fetal hemoglobin regulator in human erythroid cells
Abstract
Hemoglobin in red blood cells (RBCs) carries oxygen to the tissues. Sickle cell disease is an inherited condition that involves abnormal hemoglobin. Current treatments entail modulating the level of fetal hemoglobin expression. Grevet et al. performed a CRISPR-Cas9 screen for regulators of fetal hemoglobin in RBCs and identified heme-regulated eIF2α kinase (HRI). Depleting the kinase in RBCs led to an increase in fetal hemoglobin levels and reduced sickling of cultured human RBCs. Thus, HRI may be a therapeutic target for sickle cell disease and other hemoglobin disorders.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 20, 2018
- Source ID
- 10.1126/science.aao0932
Entities
People
- Belinda M Giardine
- Ben A. Garcia
- Carolyne J Face
- Cheryl A Keller
- Christopher R. Edwards
- David F. Posocco
- Gerd A Blobel
- Jeremy D Grevet
- Junwei Shi
- Laavanya Sankaranarayanan
- Nicole Hamagami
- Osheiza Abdulmalik
- Ross Hardison
- Saurabh K. Bhardwaj
- Simone Sidoli
- Stella T. Chou
- Stephen A. Liebhaber
- Xianjiang Lan
- Xinjun Ji
Organizations
- Children's Hospital of Philadelphia
- National Heart and Lung Institute
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of General Medical Sciences
- National Institute on Minority Health and Health Disparities
- Pennsylvania State University
- United States Department of Defense
- University of Pennsylvania