Transcriptomics,Genomics

Dataset Information

24

Dppa4 is dispensable for embryonic stem cell identity and germ cell development, but essential for embryogenesis


ABSTRACT: Dppa4 (Developmental pluripotency-associated 4) has been identified in several highprofile screens as a gene that is expressed exclusively in pluripotent cells. It encodes a nuclear protein with a SAP-like domain and appears to be associated preferentially with transcriptionally active chromatin. Its exquisite expression pattern and results of RNA interference experiments have led to speculation that Dppa4, as well as its nearby homolog Dppa2, might play essential roles in embryonic stem cell function and/or germ cell development. To rigorously assess suggested roles, we have generated Dppa4-deficient and Dppa4/Dppa2 double-deficient ES cells, as well as mice lacking Dppa4. Contrary to predictions, we find that Dppa4 is completely dispensable for ES cell identity and germ cell development. Instead, loss of Dppa4 in mice results in late embryonic/peri-natal death and striking skeletal defects with partial penetrance. Thus, surprisingly, Dppa4-deficiency affects tissues, which never transcribed the gene, and at least some loss-of-function defects manifest phenotypically at an embryonic stage long after physiologic Dppa4 expression has ceased. Concomitant with targeted gene inactivation, we have introduced into the Dppa4 locus a red fluorescent marker (tandem-dimer RFP), which is compatible with GFP-based proteins and allows non-invasive visualization of pluripotent cells and reprogramming events. Overall design: Comparison of Dppa4 knockout ES cells (CI#243.12) against Dppa4 hemizygous parental ES cell line (CI#84.2). Both cell lines were grown in presence of mouse embrionic fibroblasts as feeder cells

INSTRUMENT(S): [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array

SUBMITTER: Michael H. Walter  

PROVIDER: GSE15173 | GEO | 2009-05-01

SECONDARY ACCESSION(S): PRJNA114979

REPOSITORIES: GEO

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Publications

The pluripotency-associated gene Dppa4 is dispensable for embryonic stem cell identity and germ cell development but essential for embryogenesis.

Madan Babita B   Madan Vikas V   Weber Odile O   Tropel Philippe P   Blum Carmen C   Kieffer Emmanuelle E   Viville Stéphane S   Fehling Hans Jörg HJ  

Molecular and cellular biology 20090330 11


Dppa4 (developmental pluripotency-associated 4) has been identified in several high-profile screens as a gene that is expressed exclusively in pluripotent cells. It encodes a nuclear protein with an SAP-like domain and appears to be associated preferentially with transcriptionally active chromatin. Its exquisite expression pattern and results of RNA interference experiments have led to speculation that Dppa4, as well as its nearby homolog Dppa2, might play essential roles in embryonic stem (ES)  ...[more]

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