Jinwei Du1, Yu-Chung Yang. 1. Department of Biochemistry and Cancer Center, Case Western Reserve University, Cleveland, Ohio 44106-4935, USA.
Abstract
PURPOSE OF REVIEW: Transcription co-regulator Cited2 is essential for mouse development. Recent work has shown that Cited2 plays important roles in normal hematopoiesis in fetal liver and adult bone marrow. This review focuses on the function of Cited2 in the maintenance of hematopoietic stem cells (HSCs) and its potential role in the metabolic regulation of HSCs. RECENT FINDINGS: Fetal liver cells from Cited2 null embryos give rise to reduced numbers of hematopoietic colonies and display significantly impaired hematopoietic reconstitution capacity. In adult mice, conditional deletion of Cited2 markedly reduces the number of HSCs and compromises hematopoietic reconstitution in mice receiving a transplant of Cited2 deficient bone marrow cells. Additional deletion of Ink4a/Arf or p53 in a Cited2-deficient background restores HSC functionality. Meanwhile, Cited2 deficient HSCs display loss of quiescence, which can be partially rescued by additional deletion of hypoxia inducible factor-1α. SUMMARY: Cited2 is an essential regulator in fetal liver and adult hematopoiesis. Further studies into the function of Cited2 and the underlying mechanism in the metabolic regulation of HSCs will provide a better understanding of the connection between energy metabolism and HSC quiescence and self-renewal. Investigations of the pathologic role of Cited2 in leukemogenesis may yield useful information in developing effective therapeutic strategies.
PURPOSE OF REVIEW: Transcription co-regulator Cited2 is essential for mouse development. Recent work has shown that Cited2 plays important roles in normal hematopoiesis in fetal liver and adult bone marrow. This review focuses on the function of Cited2 in the maintenance of hematopoietic stem cells (HSCs) and its potential role in the metabolic regulation of HSCs. RECENT FINDINGS: Fetal liver cells from Cited2 null embryos give rise to reduced numbers of hematopoietic colonies and display significantly impaired hematopoietic reconstitution capacity. In adult mice, conditional deletion of Cited2 markedly reduces the number of HSCs and compromises hematopoietic reconstitution in mice receiving a transplant of Cited2 deficient bone marrow cells. Additional deletion of Ink4a/Arf or p53 in a Cited2-deficient background restores HSC functionality. Meanwhile, Cited2 deficient HSCs display loss of quiescence, which can be partially rescued by additional deletion of hypoxia inducible factor-1α. SUMMARY:Cited2 is an essential regulator in fetal liver and adult hematopoiesis. Further studies into the function of Cited2 and the underlying mechanism in the metabolic regulation of HSCs will provide a better understanding of the connection between energy metabolism and HSC quiescence and self-renewal. Investigations of the pathologic role of Cited2 in leukemogenesis may yield useful information in developing effective therapeutic strategies.
Authors: Tianwen Huang; Yasmilde Rodríguez González; Dianbo Qu; En Huang; Farzaneh Safarpour; Eugene Wang; Alvin Joselin; Doo Soon Im; Steve M Callaghan; Wassamon Boonying; Lisa Julian; Sally L Dunwoodie; Ruth S Slack; David S Park Journal: J Biol Chem Date: 2019-04-09 Impact factor: 5.157
Authors: Stéphane Prost; Francis Relouzat; Marc Spentchian; Yasmine Ouzegdouh; Joseph Saliba; Gérald Massonnet; Jean-Paul Beressi; Els Verhoeyen; Victoria Raggueneau; Benjamin Maneglier; Sylvie Castaigne; Christine Chomienne; Stany Chrétien; Philippe Rousselot; Philippe Leboulch Journal: Nature Date: 2015-09-02 Impact factor: 49.962