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E-GEOD-63830 - Functional screen for novel regulators of murine hematopoietic stem cell in vivo repopulating activity

Status
Released on 1 July 2015, last updated on 19 August 2015
Organism
Mus musculus
Samples (6)
Array (1)
Protocols (6)
Description
Although Hematopoietic Stem Cell Transplantation (HSCT) routinely treats hematologic disease, many patients experience adverse outcomes. Understanding the molecular regulation of HSC engraftment is paramount to improving HSCT regimens. Here, we executed a large-scale transplant-based functional screen for novel regulators of HSC repopulation.. Of >50 gene candidates tested, 18 were required for in vivo hematopoietic repopulation and two were detrimental to repopulation, as their loss enhanced this activity. Each Hit was validated in a second screen. Eleven Hits have never before been implicated in HSC biology. We further show that one novel Hit, Foxa3, is required for optimal engraftment as Foxa3-/- bone marrow is defective in both primary and secondary hematopoietic reconstitution. We also present evidence that Foxa3 is a novel pioneer factor in HSC. Each gene identified in our screen is a window into the cellular mechanisms that control hematopoietic reconstitution. Thus, this work represents a resource to the community to better understand these processes 3 FOXA3 KO samples are compared to 3 wt samples
Experiment type
transcription profiling by array 
Contacts
David Finkelstein <david.finkelstein@stjude.org>, Alba Cico, Angelica C Saulsberry, Himangi Marathe, Jennifer Pardieck, Ludovic Gaut, Miguel Ganuza, Per Holmfeldt, Shannon McKinney-Freeman, Trent Hall
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-63830.idf.txt
Sample and data relationshipE-GEOD-63830.sdrf.txt
Raw data (1)E-GEOD-63830.raw.1.zip
Processed data (1)E-GEOD-63830.processed.1.zip
Array designA-GEOD-16570.adf.txt
Links