C/EBPα Is Required for Long-Term Self-Renewal and Lineage Priming of Hematopoietic Stem Cells and for the Maintenance of Epigenetic Configurations in Multipotent Progenitors
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
C/EBPα Is Required for Long-Term Self-Renewal and Lineage Priming of Hematopoietic Stem Cells and for the Maintenance of Epigenetic Configurations in Multipotent Progenitors. / Hasemann, Marie S; Lauridsen, Felicia K B; Waage, Johannes; Jakobsen, Janus S; Frank, Anne-Katrine; Schuster, Mikkel B; Rapin, Nicolas Philippe Jean-Pierre; Bagger, Frederik O; Hoppe, Philipp S; Schroeder, Timm; Porse, Bo T.
I: P L o S Genetics (Online), Bind 10, Nr. 1, e1004079, 01.2014, s. 1-10.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - C/EBPα Is Required for Long-Term Self-Renewal and Lineage Priming of Hematopoietic Stem Cells and for the Maintenance of Epigenetic Configurations in Multipotent Progenitors
AU - Hasemann, Marie S
AU - Lauridsen, Felicia K B
AU - Waage, Johannes
AU - Jakobsen, Janus S
AU - Frank, Anne-Katrine
AU - Schuster, Mikkel B
AU - Rapin, Nicolas Philippe Jean-Pierre
AU - Bagger, Frederik O
AU - Hoppe, Philipp S
AU - Schroeder, Timm
AU - Porse, Bo T
PY - 2014/1
Y1 - 2014/1
N2 - Transcription factors are key regulators of hematopoietic stem cells (HSCs) and act through their ability to bind DNA and impact on gene transcription. Their functions are interpreted in the complex landscape of chromatin, but current knowledge on how this is achieved is very limited. C/EBPα is an important transcriptional regulator of hematopoiesis, but its potential functions in HSCs have remained elusive. Here we report that C/EBPα serves to protect adult HSCs from apoptosis and to maintain their quiescent state. Consequently, deletion of Cebpa is associated with loss of self-renewal and HSC exhaustion. By combining gene expression analysis with genome-wide assessment of C/EBPα binding and epigenetic configurations, we show that C/EBPα acts to modulate the epigenetic states of genes belonging to molecular pathways important for HSC function. Moreover, our data suggest that C/EBPα acts as a priming factor at the HSC level where it actively promotes myeloid differentiation and counteracts lymphoid lineage choice. Taken together, our results show that C/EBPα is a key regulator of HSC biology, which influences the epigenetic landscape of HSCs in order to balance different cell fate options.
AB - Transcription factors are key regulators of hematopoietic stem cells (HSCs) and act through their ability to bind DNA and impact on gene transcription. Their functions are interpreted in the complex landscape of chromatin, but current knowledge on how this is achieved is very limited. C/EBPα is an important transcriptional regulator of hematopoiesis, but its potential functions in HSCs have remained elusive. Here we report that C/EBPα serves to protect adult HSCs from apoptosis and to maintain their quiescent state. Consequently, deletion of Cebpa is associated with loss of self-renewal and HSC exhaustion. By combining gene expression analysis with genome-wide assessment of C/EBPα binding and epigenetic configurations, we show that C/EBPα acts to modulate the epigenetic states of genes belonging to molecular pathways important for HSC function. Moreover, our data suggest that C/EBPα acts as a priming factor at the HSC level where it actively promotes myeloid differentiation and counteracts lymphoid lineage choice. Taken together, our results show that C/EBPα is a key regulator of HSC biology, which influences the epigenetic landscape of HSCs in order to balance different cell fate options.
U2 - 10.1371/journal.pgen.1004079
DO - 10.1371/journal.pgen.1004079
M3 - Journal article
C2 - 24415956
VL - 10
SP - 1
EP - 10
JO - P L o S Genetics
JF - P L o S Genetics
SN - 1553-7390
IS - 1
M1 - e1004079
ER -
ID: 99236732