Transcriptomics

Dataset Information

4

Functional screen for novel regulators of murine hematopoietic stem cell in vivo repopulating activity


ABSTRACT: 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

ORGANISM(S): Mus musculus  

SUBMITTER: Himangi Marathe   Jennifer Pardieck  Ludovic Gaut  Trent Hall  Alba Cico  Angelica C Saulsberry  Miguel Ganuza  David Finkelstein  Shannon McKinney-Freeman  Per Holmfeldt 

PROVIDER: E-GEOD-63830 | ArrayExpress | 2015-07-01

SECONDARY ACCESSION(S): GSE63830PRJNA269178

REPOSITORIES: GEO, ArrayExpress

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