title: Exosome complex orchestrates developmental signaling to balance proliferation and differentiation during erythropoiesis.
abstract: Since the highly conserved exosome complex mediates the degradation and processing of multiple classes of RNAs, it almost certainly controls diverse biological processes. How this post-transcriptional RNA-regulatory machine impacts cell fate decisions and differentiation is poorly understood. Previously, we demonstrated that exosome complex subunits confer an erythroid maturation barricade, and the erythroid transcription factor GATA-1 dismantles the barricade by transcriptionally repressing the cognate genes. While dissecting requirements for the maturation barricade inMus musculus, we discovered that the exosome complex is a vital determinant of a developmental signaling transition that dictates proliferation/amplification versus differentiation. Exosome complex integrity in erythroid precursor cells ensures Kit receptor tyrosine kinase expression and stem cell factor/Kit signaling, while preventing responsiveness to erythropoietin-instigated signals that promote differentiation. Functioning as a gatekeeper of this developmental signaling transition, the exosome complex controls the massive production of erythroid cells that ensures organismal survival in homeostatic and stress contexts.
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, United States.|UW-Madison Blood Research Program, University of Wisconsin School of Medicine and Public Health, Madison, United States.|Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, United States.
authors.forename: Skye C
authors.initials: SC
authors.lastname: McIver
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, United States.|UW-Madison Blood Research Program, University of Wisconsin School of Medicine and Public Health, Madison, United States.|Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, United States.
authors.forename: Koichi R
authors.initials: KR
authors.lastname: Katsumura
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, United States.|UW-Madison Blood Research Program, University of Wisconsin School of Medicine and Public Health, Madison, United States.|Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, United States.
authors.forename: Elsa
authors.initials: E
authors.lastname: Davids
authors.affiliation: Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, United States.|Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, United States.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, United States.|UW-Madison Blood Research Program, University of Wisconsin School of Medicine and Public Health, Madison, United States.|Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, United States.
authors.forename: Yoon-A
authors.initials: YA
authors.lastname: Kang
authors.affiliation: Department of Pathology, University of Wisconsin School of Medicine and Public Health, Madison, United States.
authors.forename: David
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, United States.|UW-Madison Blood Research Program, University of Wisconsin School of Medicine and Public Health, Madison, United States.|Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, United States.
authors.forename: Emery H
authors.identifier: http://orcid.org/0000-0002-1151-5654
authors.initials: EH
authors.lastname: Bresnick
keywords: cell biology; erythroid; mouse; progenitor; signaling; transcription