Premature activation of immune transcription programs in autoimmune-predisposed mouse embryonic stem cells and blastocysts
Abstract: Autoimmune diabetes is a complex multifactorial disease with genetic and environmental factors playing pivotal roles. While many genes associated with the risk of diabetes have been identified to date, the mechanisms by which external triggers contribute to the genetic predisposition remain unclear. Here, we derived embryonic stem (ES) cell lines from diabetes-prone non-obese diabetic (NOD) and healthy C57BL/6 (B6) mice. While overall pluripotency markers were indistinguishable between newly derived NOD and B6 ES cells, we discovered several differentially expressed genes that normally are not expressed in ES cells. Several genes that reside in previously identified insulin-dependent diabetics (Idd) genomic regions were up-regulated in NOD ES cells. Gene set enrichment analysis showed that different groups of genes associated with immune functions are differentially expressed in NOD. Transcriptomic analysis of NOD blastocysts validated several differentially overexpressed Idd genes compared to B6. Genome-wide mapping of active histone modifications using ChIP-Seq supports active expression as the promoters and enhancers of activated genes are also marked by active histone modifications. We have also found that NOD ES cells secrete more inflammatory cytokines. Our data suggest that the known genetic predisposition of NOD to autoimmune diabetes leads to epigenetic instability of several Idd regions
- Location
-
Deutsche Nationalbibliothek Frankfurt am Main
- Extent
-
Online-Ressource
- Language
-
Englisch
- Notes
-
International journal of molecular sciences. - 21, 16 (2020) , 5743, ISSN: 1422-0067
- Keyword
-
Embryonale Stammzelle
Autoimmunität
Veranlagung
Cytokine
Chemokine
- Event
-
Veröffentlichung
- (where)
-
Freiburg
- (who)
-
Universität
- (when)
-
2020
- Creator
-
Kirak, Oktay
Ke, Eugene
Yang, Kevin Y.
Schwarz, Anna
Plate, Lars
Nham, Amy
Abadejos, Justin R.
Valencia, Anna M.
Wiseman, R. Luke
Lui, Kathy O.
Ku, Manching
- DOI
-
10.3390/ijms21165743
- URN
-
urn:nbn:de:bsz:25-freidok-1668751
- Rights
-
Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
-
14.08.2025, 10:56 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Kirak, Oktay
- Ke, Eugene
- Yang, Kevin Y.
- Schwarz, Anna
- Plate, Lars
- Nham, Amy
- Abadejos, Justin R.
- Valencia, Anna M.
- Wiseman, R. Luke
- Lui, Kathy O.
- Ku, Manching
- Universität
Time of origin
- 2020
Other Objects (12)
Premature immunosenescence in patients with autoimmune lymphoproliferative immunodeficiencies
Transcription factor expression landscape in Drosophila embryonic cell lines
Interplay of transcription factors and microRNAs during embryonic hematopoiesis
Multiple enhancer regions govern the transcription of CCN2 during embryonic development
Rbpj direct regulation of Atoh7 transcription in the embryonic mouse retina
Combinatorial transcription factor activities on open chromatin induce embryonic heterogeneity in vertebrates
Premature burial
Blocking premature reverse transcription fails to rescue the HIV-1 nucleocapsid-mutant replication defect
The role of RNA-polymerase II transcription in embryonic nucleologenesis by bovine embryos
Expression of the transcription factor, TFII-I, during post-implantation mouse embryonic development
Tissue-location-specific transcription programs drive tumor dependencies in colon cancer
The endogenous retrovirus ENS-1 provides active binding sites for transcription factors in embryonic stem cells that specify extra embryonic tissue
Premature immunosenescence in patients with autoimmune lymphoproliferative immunodeficiencies
Transcription factor expression landscape in Drosophila embryonic cell lines
Interplay of transcription factors and microRNAs during embryonic hematopoiesis
Multiple enhancer regions govern the transcription of CCN2 during embryonic development
Rbpj direct regulation of Atoh7 transcription in the embryonic mouse retina
Combinatorial transcription factor activities on open chromatin induce embryonic heterogeneity in vertebrates
Premature burial
Blocking premature reverse transcription fails to rescue the HIV-1 nucleocapsid-mutant replication defect
The role of RNA-polymerase II transcription in embryonic nucleologenesis by bovine embryos
Expression of the transcription factor, TFII-I, during post-implantation mouse embryonic development
Tissue-location-specific transcription programs drive tumor dependencies in colon cancer
The endogenous retrovirus ENS-1 provides active binding sites for transcription factors in embryonic stem cells that specify extra embryonic tissue
Premature immunosenescence in patients with autoimmune lymphoproliferative immunodeficiencies
Transcription factor expression landscape in Drosophila embryonic cell lines
Interplay of transcription factors and microRNAs during embryonic hematopoiesis
Multiple enhancer regions govern the transcription of CCN2 during embryonic development
Rbpj direct regulation of Atoh7 transcription in the embryonic mouse retina
Combinatorial transcription factor activities on open chromatin induce embryonic heterogeneity in vertebrates
Premature burial
Blocking premature reverse transcription fails to rescue the HIV-1 nucleocapsid-mutant replication defect
The role of RNA-polymerase II transcription in embryonic nucleologenesis by bovine embryos
Expression of the transcription factor, TFII-I, during post-implantation mouse embryonic development
Tissue-location-specific transcription programs drive tumor dependencies in colon cancer