title: Ataxin1L is a regulator of HSC function highlighting the utility of cross-tissue comparisons for gene discovery.
abstract: Hematopoietic stem cells (HSCs) are rare quiescent cells that continuously replenish the cellular components of the peripheral blood. Observing that the ataxia-associated gene Ataxin-1-like (Atxn1L) was highly expressed in HSCs, we examined its role in HSC function through in vitro and in vivo assays. Mice lacking Atxn1L had greater numbers of HSCs that regenerated the blood more quickly than their wild-type counterparts. Molecular analyses indicated Atxn1L null HSCs had gene expression changes that regulate a program consistent with their higher level of proliferation, suggesting that Atxn1L is a novel regulator of HSC quiescence. To determine if additional brain-associated genes were candidates for hematologic regulation, we examined genes encoding proteins from autism- and ataxia-associated protein-protein interaction networks for their representation in hematopoietic cell populations. The interactomes were found to be highly enriched for proteins encoded by genes specifically expressed in HSCs relative to their differentiated progeny. Our data suggest a heretofore unappreciated similarity between regulatory modules in the brain and HSCs, offering a new strategy for novel gene discovery in both systems.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Juliette J
authors.initials: JJ
authors.lastname: Kahle
authors.forename: George P
authors.initials: GP
authors.lastname: Souroullas
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.forename: Fabian
authors.initials: F
authors.lastname: Zohren
authors.forename: Yoontae
authors.initials: Y
authors.lastname: Lee
authors.forename: Chad A
authors.initials: CA
authors.lastname: Shaw
authors.forename: Huda Y
authors.initials: HY
authors.lastname: Zoghbi
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Goodell
mesh_terms: D000818:Animals; D001259:Ataxia / Q000235:genetics / Q000378:metabolism; D000067696:Ataxin-1; D000067528:Ataxins; D001321:Autistic Disorder / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D060066:Protein Interaction Maps
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins
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