biostudies-literatureSengupta ANCRR NIH HHSNHLBI NIH HHSNIMHD NIH HHS145-54https://www.ebi.ac.uk/biostudies/studies/S-EPMC4732296biostudies-literatureUnknown129(1)Appropriate diversification of cellular lineages from multi-potent progenitors is essential for normal development and homeostasis. The specification of erythroid and megakaryocytic lineages represents an especially vital developmental event whose molecular regulation remains incompletely defined. We now demonstrate the role of Rgs18, a GTPase-activating protein and transcriptional target of the repressor Gfi1b, in regulating these processes in mouse and human cells. Gfi1b stringently represses Rgs18 expression in erythroid cells, whereas, during megakaryocytic differentiation, declining Gfi1b levels facilitate a robust induction of Rgs18. Concordantly, alterations in Rgs18 expression produce disparate outcomes by augmenting megakaryocytic and potently suppressing erythroid differentiationJournal of cell scienceReciprocal regulation of alternative lineages by Rgs18 and its transcriptional repressor Gfi1b.PMC47322965SC1HL104638SC1 HL1046388G12MD007603-27G12RR03060-26A1G12 RR003060G12 MD007603Saleque SUpadhyay GSengupta ASen SfalseReciprocal regulation of alternative lineages by Rgs18 and its transcriptional repressor Gfi1b.Appropriate diversification of cellular lineages from multi-potent progenitors is essential for normal development and homeostasis. The specification of erythroid and megakaryocytic lineages represents an especially vital developmental event whose molecular regulation remains incompletely defined. We now demonstrate the role of Rgs18, a GTPase-activating protein and transcriptional target of the repressor Gfi1b, in regulating these processes in mouse and human cells. Gfi1b stringently represses Rgs18 expression in erythroid cells, whereas, during megakaryocytic differentiation, declining Gfi1b levels facilitate a robust induction of Rgs18. Concordantly, alterations in Rgs18 expression produce disparate outcomes by augmenting megakaryocytic and potently suppressing erythroid differentiation2016-01-01T00:00:00Z2016 Jan2025-05-29T22:24:06.594Z2019-06-06T15:21:20ZS-EPMC47322962656721410.1242/jcs.177519