Domain-focused CRISPR screen identifies HRI as a fetal hemoglobin regulator in human erythroid cells

Autor:	Ross C. Hardison, Saurabh K. Bhardwaj, Carolyne J. Face, Stella T. Chou, Christopher R. Edwards, Stephen A. Liebhaber, Gerd A. Blobel, Xianjiang Lan, Ben A. Garcia, Junwei Shi, Laavanya Sankaranarayanan, David Posocco, Simone Sidoli, Belinda Giardine, Nicole Hamagami, Osheiza Abdulmalik, Jeremy D. Grevet, Cheryl A. Keller, Xinjun Ji
Rok vydání:	2018
Předmět:	0301 basic medicine congenital hereditary and neonatal diseases and abnormalities Cell Repressor Anemia Sickle Cell Biology Article Cell Line eIF-2 Kinase 03 medical and health sciences Erythroid Cells hemic and lymphatic diseases Fetal hemoglobin medicine Humans Genetic Testing Molecular Targeted Therapy Fetal Hemoglobin Regulation of gene expression Multidisciplinary Kinase Nuclear Proteins RNA Cell biology Repressor Proteins 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Cell culture CRISPR-Cas Systems Carrier Proteins RNA Guide Kinetoplastida Genetic screen
Zdroj:	Science. 361:285-290
ISSN:	1095-9203 0036-8075
Popis:	A CRISPR screen for RBC regulators 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. Science , this issue p. 285
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5109cfea70f05b8aa327d5970f3421e6 https://doi.org/10.1126/science.aao0932 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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