In vivo deficiency of both C/EBPβ and C/EBPε results in highly defective myeloid differentiation and lack of cytokine response.
The CCAAT/enhancer binding proteins (C/EBPs) are transcription factors involved in hematopoietic cell development and induction of several inflammatory mediators. Here, we generated C/EBPβ and C/EBPε double-knockout (bbee) mice and compared their phenotypes to those of single deficient (bbEE and BBe...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2010-11-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0015419&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849734917903089664 |
|---|---|
| author | Tadayuki Akagi Nils H Thoennissen Ann George Gay Crooks Jee Hoon Song Ryoko Okamoto Daniel Nowak Adrian F Gombart H Phillip Koeffler |
| author_facet | Tadayuki Akagi Nils H Thoennissen Ann George Gay Crooks Jee Hoon Song Ryoko Okamoto Daniel Nowak Adrian F Gombart H Phillip Koeffler |
| author_sort | Tadayuki Akagi |
| collection | DOAJ |
| description | The CCAAT/enhancer binding proteins (C/EBPs) are transcription factors involved in hematopoietic cell development and induction of several inflammatory mediators. Here, we generated C/EBPβ and C/EBPε double-knockout (bbee) mice and compared their phenotypes to those of single deficient (bbEE and BBee) and wild-type (BBEE) mice. The bbee mice were highly susceptible to fatal infections and died within 2-3 months. Morphologically, their neutrophils were blocked at the myelocytes/metamyelocytes stage, and clonogenic assays of bone marrow cells indicated a significant decrease in the number of myeloid colonies of the bbee mice. In addition, the proportion of hematopoietic progenitor cells [Lin(-)Sca1(+)c-Kit(+)] in the bone marrow of the bbee mice was significantly increased, reflecting the defective differentiation of the myeloid compartment. Furthermore, microarray expression analysis of LPS- and IFNγ-activated bone marrow-derived macrophages from bbee compared to single knockout mice revealed decreased expression of essential immune response-related genes and networks, including some direct C/EBP-targets such as Marco and Clec4e. Overall, the phenotype of the bbee mice is distinct from either the bbEE or BBee mice, demonstrating that both transcription factors are crucial for the maturation of neutrophils and macrophages, as well as the innate immune system, and can at least in part compensate for each other in the single knockout mice. |
| format | Article |
| id | doaj-art-ff8977fe1591483fae0b70e6a29f35ba |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2010-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-ff8977fe1591483fae0b70e6a29f35ba2025-08-20T03:07:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-11-01511e1541910.1371/journal.pone.0015419In vivo deficiency of both C/EBPβ and C/EBPε results in highly defective myeloid differentiation and lack of cytokine response.Tadayuki AkagiNils H ThoennissenAnn GeorgeGay CrooksJee Hoon SongRyoko OkamotoDaniel NowakAdrian F GombartH Phillip KoefflerThe CCAAT/enhancer binding proteins (C/EBPs) are transcription factors involved in hematopoietic cell development and induction of several inflammatory mediators. Here, we generated C/EBPβ and C/EBPε double-knockout (bbee) mice and compared their phenotypes to those of single deficient (bbEE and BBee) and wild-type (BBEE) mice. The bbee mice were highly susceptible to fatal infections and died within 2-3 months. Morphologically, their neutrophils were blocked at the myelocytes/metamyelocytes stage, and clonogenic assays of bone marrow cells indicated a significant decrease in the number of myeloid colonies of the bbee mice. In addition, the proportion of hematopoietic progenitor cells [Lin(-)Sca1(+)c-Kit(+)] in the bone marrow of the bbee mice was significantly increased, reflecting the defective differentiation of the myeloid compartment. Furthermore, microarray expression analysis of LPS- and IFNγ-activated bone marrow-derived macrophages from bbee compared to single knockout mice revealed decreased expression of essential immune response-related genes and networks, including some direct C/EBP-targets such as Marco and Clec4e. Overall, the phenotype of the bbee mice is distinct from either the bbEE or BBee mice, demonstrating that both transcription factors are crucial for the maturation of neutrophils and macrophages, as well as the innate immune system, and can at least in part compensate for each other in the single knockout mice.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0015419&type=printable |
| spellingShingle | Tadayuki Akagi Nils H Thoennissen Ann George Gay Crooks Jee Hoon Song Ryoko Okamoto Daniel Nowak Adrian F Gombart H Phillip Koeffler In vivo deficiency of both C/EBPβ and C/EBPε results in highly defective myeloid differentiation and lack of cytokine response. PLoS ONE |
| title | In vivo deficiency of both C/EBPβ and C/EBPε results in highly defective myeloid differentiation and lack of cytokine response. |
| title_full | In vivo deficiency of both C/EBPβ and C/EBPε results in highly defective myeloid differentiation and lack of cytokine response. |
| title_fullStr | In vivo deficiency of both C/EBPβ and C/EBPε results in highly defective myeloid differentiation and lack of cytokine response. |
| title_full_unstemmed | In vivo deficiency of both C/EBPβ and C/EBPε results in highly defective myeloid differentiation and lack of cytokine response. |
| title_short | In vivo deficiency of both C/EBPβ and C/EBPε results in highly defective myeloid differentiation and lack of cytokine response. |
| title_sort | in vivo deficiency of both c ebpβ and c ebpε results in highly defective myeloid differentiation and lack of cytokine response |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0015419&type=printable |
| work_keys_str_mv | AT tadayukiakagi invivodeficiencyofbothcebpbandcebperesultsinhighlydefectivemyeloiddifferentiationandlackofcytokineresponse AT nilshthoennissen invivodeficiencyofbothcebpbandcebperesultsinhighlydefectivemyeloiddifferentiationandlackofcytokineresponse AT anngeorge invivodeficiencyofbothcebpbandcebperesultsinhighlydefectivemyeloiddifferentiationandlackofcytokineresponse AT gaycrooks invivodeficiencyofbothcebpbandcebperesultsinhighlydefectivemyeloiddifferentiationandlackofcytokineresponse AT jeehoonsong invivodeficiencyofbothcebpbandcebperesultsinhighlydefectivemyeloiddifferentiationandlackofcytokineresponse AT ryokookamoto invivodeficiencyofbothcebpbandcebperesultsinhighlydefectivemyeloiddifferentiationandlackofcytokineresponse AT danielnowak invivodeficiencyofbothcebpbandcebperesultsinhighlydefectivemyeloiddifferentiationandlackofcytokineresponse AT adrianfgombart invivodeficiencyofbothcebpbandcebperesultsinhighlydefectivemyeloiddifferentiationandlackofcytokineresponse AT hphillipkoeffler invivodeficiencyofbothcebpbandcebperesultsinhighlydefectivemyeloiddifferentiationandlackofcytokineresponse |