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LIM domain binding protein 1 regulates a transcriptional program essential for hematopoietic stem cell maintenance

ABSTRACT: We used ChIP-Seq to map Ldb1, Scl and Gata2 binding sites in mouse hematopoietic progenitor cells (HPCs). Together with functional studies using conventional and conditional Ldb1 deficient mouse models and bioinformatics analysis, we systematically determined a transcriptional program controlled by Ldb1 complexes in HSC maintenance. To evaluate the role of Ldb1 in hematopoietic stem cell maintenance.

ORGANISM(S): Mus musculus

SUBMITTER: Raja Jothi

PROVIDER: E-GEOD-26031 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Nuclear adaptor Ldb1 regulates a transcriptional program essential for the maintenance of hematopoietic stem cells.

Li LiQi L Jothi Raja R Cui Kairong K Lee Jan Y JY Cohen Tsadok T Gorivodsky Marat M Tzchori Itai I Zhao Yangu Y Hayes Sandra M SM Bresnick Emery H EH Zhao Keji K Westphal Heiner H Love Paul E PE

Nature immunology 20101226 2

The nuclear adaptor Ldb1 functions as a core component of multiprotein transcription complexes that regulate differentiation in diverse cell types. In the hematopoietic lineage, Ldb1 forms a complex with the non-DNA-binding adaptor Lmo2 and the transcription factors E2A, Scl and GATA-1 (or GATA-2). Here we demonstrate a critical and continuous requirement for Ldb1 in the maintenance of both fetal and adult mouse hematopoietic stem cells (HSCs). Deletion of Ldb1 in hematopoietic progenitors resul ...[more]

PMID: 21186366

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Ldb1-nucleated transcription complexes function as primary mediators of erythroid gene activation

Project description:We used ChIP-Seq to map Ldb1, Scl and Gata1 binding sites in mouse total bone marrow cells. Together with functional studies comparing gene expression in Murine Erythroleukemia (MEL) cells expressing Ldb1 shRNA or control shRNA and bioinformatics analysis, we systematically determined the transcriptional program controlled by Ldb1 complexes in erythropoiesis. This represents the ChIP-Seq component of the study only To evaluate the role of Ldb1complexes in erythroid gene activation

2013-04-29 | E-GEOD-42843 | biostudies-arrayexpress

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Project description:The first site exhibiting hematopoietic activity in mammalian development is the yolk sac blood island, which originates from the hemangioblast. Here we performed differentiation assays, as well as genome-wide molecular and functional studies in BL-CFCs to gain insight into the function of the essential Ldb1 factor in early primitive hematopoietic development. We show that the previously reported lack of yolk sac hematopoiesis and vascular development in Ldb1-/- mouse result from a decreased number of hemangioblasts and a block in their ability to differentiate into erythroid and endothelial progenitor cells. Transcriptome analysis and correlation with the genome wide binding pattern of Ldb1 in hemangioblasts revealed a number of direct target genes and pathways misregulated in the absence of Ldb1. The regulation of essential developmental factors by Ldb1 defines it as an upstream transcriptional regulator of hematopoietic/endothelial development. We show the complex interplay that exists between transcription factors and signaling pathways during the very early stages of hematopoietic/endothelial development and the specific signalling occurring in hemangioblasts in contrast to more advanced hematopoietic developmental stages. Finally, by revealing novel genes and pathways, not previously associated with early development, our study provides novel candidate targets to manipulate the differentiation of hematopoietic and/or endothelial cells. We used microarrays to detail the global programme of gene expression underlying the Ldb1+/+ and Ldb1-/- in Flk1+ cells. RNA was isolated from Ldb1+/+ and Ldb1-/- Flk1+ cells with the QIAGEN RNeasy Mini Kit and integrity was checked on the Agilent 2100 Bioanalyzer. RNA was converted to biotin-labelled cRNA, hybridised on the Mouse Genome 430 2.0 Array and analyzed with the Affymetrix GeneChipÂ® Scanner 3000 according to the manufacturer protocol.

2013-02-09 | E-GEOD-43042 | biostudies-arrayexpress

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2013-02-09 | E-GEOD-43041 | biostudies-arrayexpress

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2011-01-04 | GSE26031 | GEO

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2014-07-02 | E-GEOD-54549 | biostudies-arrayexpress

Genome-wide mapping of the transcription factor GABP-alpha binding in human CD34+CD133+ hematopoietic progenitor cells.

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2010-12-10 | E-GEOD-24933 | biostudies-arrayexpress

Expression changes in MEL cells upon differentiation and Ldb1 knockdown

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2012-12-11 | E-GEOD-42839 | biostudies-arrayexpress

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2015-02-03 | E-GEOD-64483 | biostudies-arrayexpress

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