Transcriptomics

Dataset Information

62

Comprehensive expression profiling across primary fetal liver terminal erythroid differentiation


ABSTRACT: Primary murine fetal liver cells were freshly isolated from day e14.5 livers and then sorted for successive differentiation stages by Ter119 and CD71 surface expression (ranging from double-negative CFU-Es to Ter-119 positive enucleated erythrocytes) [Zhang, et al. Blood. 2003 Dec 1; 102(12):3938-46]. RNA isolated from each freshly isolated, stage-sorted population was reverse-transcribed, labelled, and then hybridized onto 3' oligo Affymetrix arrays. Important erythroid specific genes as well as the proteins that regulate them were elucidated through this profiling based on coexpression and differential expression patterns as well as by extracting specific GO categories of genes (such as DNA-binding proteins). Abstract (submitted paper): rationale for expression profiling Gene-targeting experiments report that the homeodomain-interacting protein kinases 1 and 2, Hipk1 and Hipk2, are essential but redundant in hematopoietic development—because Hipk1/Hipk2 double-deficient animals exhibit severe defects in hematopoiesis and vasculogenesis while the single knockouts do not. These serine-threonine kinases phosphorylate, and consequently modify the functions of, several important hematopoietic transcription factors and cofactors. Here we show that Hipk2 knockdown alone plays a significant role in terminal fetal liver erythroid differentiation. Hipk1 and Hipk2 are highly induced during primary mouse fetal liver erythropoiesis. Specific knockdown of Hipk2 inhibits terminal erythroid cell proliferation—explained in part by impaired cell cycle progression as well as increased apoptosis—and terminal enucleation as well as the accumulation of hemoglobin. Hipk2 knockdown also reduces the transcription of many genes involved in proliferation and apoptosis as well as important, erythroid-specific genes involved in hemoglobin biosynthesis—such as alpha-globin and mitoferrin 1—demonstrating that Hipk2 plays an important role in some but not all aspects of normal terminal erythroid differentiation.

ORGANISM(S): Mus musculus  

SUBMITTER: Karly Burke   Harvey Lodish  Shilpa Manohar Hattangadi  Shilpa M Hattangadi 

PROVIDER: E-GEOD-20391 | ArrayExpress | 2010-07-08

SECONDARY ACCESSION(S): GSE20391PRJNA125517

REPOSITORIES: GEO, ArrayExpress

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Publications

Homeodomain-interacting protein kinase 2 plays an important role in normal terminal erythroid differentiation.

Hattangadi Shilpa M SM   Burke Karly A KA   Lodish Harvey F HF  

Blood 20100315 23


Gene-targeting experiments report that the homeodomain-interacting protein kinases 1 and 2, Hipk1 and Hipk2, are essential but redundant in hematopoietic development because Hipk1/Hipk2 double-deficient animals exhibit severe defects in hematopoiesis and vasculogenesis, whereas the single knockouts do not. These serine-threonine kinases phosphorylate and consequently modify the functions of several important hematopoietic transcription factors and cofactors. Here we show that Hipk2 knockdown alo  ...[more]

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