Transcriptional repressor Gfi1 integrates cytokine-receptor signals controlling B-cell differentiation.
Hematopoietic stem cell differentiation is specified by cytokines and transcription factors, but the mechanisms controlling instructive and permissive signalling networks are poorly understood. We provide evidence that CLP1-dependent IL7-receptor mediated B cell differentiation is critically controlled by the transcriptional repressor Gfi1. Gfi1-deficient progenitor B cells show global defects in IL7Ralpha-dependent signal cascades. Consequently, IL7-dependent trophic, proliferative and differentiation-inducing responses of progenitor B cells are perturbed. Gfi1 directly regulates expression levels of IL7Ralpha and indirectly controls STAT5 signalling via expression of SOCS3. Thus, Gfi1 selectively specifies IL7-dependent development of B cells from CLP1 progenitors, providing clues to the transcriptional networks integrating cytokine signals and lymphoid differentiation.
Rathinam
Chozhavendan
C
Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany.
Klein
Christoph
C
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D015851:Interleukin-7 / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics*; D020395:Receptors, Interleukin-7 / Q000235:genetics*; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics*; D019089:Stem Cell Factor / Q000494:pharmacology; D014158:Transcription, Genetic
C486395:Gfi1b protein, mouse; D015851:Interleukin-7; D011518:Proto-Oncogene Proteins; D020395:Receptors, Interleukin-7; D012097:Repressor Proteins; D019089:Stem Cell Factor