Linked Life Data

21084719

Source:http://linkedlifedata.com/resource/pubmed/id/21084719

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
58
pubmed:dateCreated
2010-11-18
pubmed:abstractText
Globoid cell leukodystrophy (GLD; also known as Krabbe disease) is an invariably fatal lysosomal storage disorder caused by mutations in the galactocerebrosidase (GALC) gene. Hematopoietic stem cell (HSC)-based gene therapy is being explored for GLD; however, we found that forced GALC expression was toxic to HSCs and early progenitors, highlighting the need for improved regulation of vector expression. We used a genetic reporter strategy based on lentiviral vectors to detect microRNA activity in hematopoietic cells at single-cell resolution. We report that miR-126 and miR-130a were expressed in HSCs and early progenitors from both mice and humans, but not in differentiated progeny. Moreover, repopulating HSCs could be purified solely on the basis of miRNA expression, providing a new method relevant for human HSC isolation. By incorporating miR-126 target sequences into a GALC-expressing vector, we suppressed GALC expression in HSCs while maintaining robust expression in mature hematopoietic cells. This approach protected HSCs from GALC toxicity and allowed successful treatment of a mouse GLD model, providing a rationale to explore HSC-based gene therapy for GLD.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1946-6242
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
58ra84
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Identification of hematopoietic stem cell-specific miRNAs enables gene therapy of globoid cell leukodystrophy.
pubmed:affiliation
San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan 20132, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't