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.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Kahle JJ,Souroullas GP,Yu P,Zohren F,Lee Y,Shaw CA,Zoghbi HY,Goodell MAdoi
10.1371/journal.pgen.1003359subject
Has Abstractpub_date
2013-03-01 00:00:00pages
e1003359issue
3eissn
1553-7390issn
1553-7404pii
PGENETICS-D-12-02559journal_volume
9pub_type
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