scholarly journals Expression of Scl in mesoderm rescues hematopoiesis in the absence of Oct-4

Blood ◽  
2009 ◽  
Vol 114 (1) ◽  
pp. 60-63 ◽  
Author(s):  
Kimi Y. Kong ◽  
Elizabeth A. Williamson ◽  
Jason H. Rogers ◽  
Tam Tran ◽  
Robert Hromas ◽  
...  

Abstract In embryonic stem cells, Oct-4 concentration is critical in determining the development of endoderm, mesoderm, and trophectoderm. Although Oct-4 expression is essential for mesoderm development, it is unclear whether it has a role in the development of specific mesodermal tissues. In this study, we have examined the importance of Oct-4 in the generation of hematopoietic cells using an inducible Oct-4 ESC line. We demonstrate that Oct-4 has a role in supporting hematopoiesis after specifying brachyury-positive mesoderm. When we suppressed Oct-4 expression before or after mesoderm specification, no hematopoietic cells are detected. However, hematopoiesis can be rescued in the absence of Oct-4 after mesoderm specification if the essential hematopoietic transcription factor stem cell leukemia is expressed. Our results suggest that, for hematopoiesis to occur, Oct-4 is required for the initial specification of mesoderm and subsequently is required for the development of hematopoietic cells from uncommitted mesoderm.

2012 ◽  
Vol 9 (2) ◽  
pp. 88-100 ◽  
Author(s):  
Yuriy Orlov ◽  
Han Xu ◽  
Dmitri Afonnikov ◽  
Bing Lim ◽  
Jian-Chien Heng ◽  
...  

Summary Advances in high throughput sequencing technology have enabled the identification of transcription factor (TF) binding sites in genome scale. TF binding studies are important for medical applications and stem cell research. Somatic cells can be reprogrammed to a pluripotent state by the combined introduction of factors such as Oct4, Sox2, c-Myc, Klf4. These reprogrammed cells share many characteristics with embryonic stem cells (ESCs) and are known as induced pluripotent stem cells (iPSCs). The signaling requirements for maintenance of human and murine embryonic stem cells (ESCs) differ considerably. Genome wide ChIP-seq TF binding maps in mouse stem cells include Oct4, Sox2, Nanog, Tbx3, Smad2 as well as group of other factors. ChIP-seq allows study of new candidate transcription factors for reprogramming. It was shown that Nr5a2 could replace Oct4 for reprogramming. Epigenetic modifications play important role in regulation of gene expression adding additional complexity to transcription network functioning. We have studied associations between different histone modification using published data together with RNA Pol II sites. We found strong associations between activation marks and TF binding sites and present it qualitatively. To meet issues of statistical analysis of genome ChIP-sequencing maps we developed computer program to filter out noise signals and find significant association between binding site affinity and number of sequence reads. The data provide new insights into the function of chromatin organization and regulation in stem cells.


Blood ◽  
2001 ◽  
Vol 98 (7) ◽  
pp. 2028-2038 ◽  
Author(s):  
Zheng Tu ◽  
John M. Ninos ◽  
Zhengyu Ma ◽  
Jia-Wang Wang ◽  
Maria P. Lemos ◽  
...  

SH2–containing inositol 5′-phosphatase (SHIP) modulates the activation of immune cells after recruitment to the membrane by Shc and the cytoplasmic tails of receptors. A novel SHIP isoform of approximately 104 kd expressed in primitive stem cell populations (s-SHIP) is described. It was found that s-SHIP is expressed in totipotent embryonic stem cells to the exclusion of the 145-kd SHIP isoform expressed in differentiated hematopoietic cells. s-SHIP is also expressed in primitive hematopoietic stem cells, but not in lineage-committed hematopoietic cells. In embryonic stem cells, s-SHIP partners with the adapter protein Grb2 without tyrosine phosphorylation and is present constitutively at the cell membrane. It is postulated that s-SHIP modulates the activation threshold of primitive stem cell populations.


2006 ◽  
Vol 26 (7) ◽  
pp. 2615-2625 ◽  
Author(s):  
John E. Pimanda ◽  
Lev Silberstein ◽  
Massimo Dominici ◽  
Benjamin Dekel ◽  
Mark Bowen ◽  
...  

ABSTRACT Blood and vascular cells are generated during early embryogenesis from a common precursor, the hemangioblast. The stem cell leukemia gene (SCL/tal 1) encodes a basic helix-loop-helix transcription factor that is essential for the normal development of blood progenitors and blood vessels. We have previously characterized a panel of SCL enhancers including the +19 element, which directs expression to hematopoietic stem cells and endothelium. Here we demonstrate that SCL is expressed in bone primordia during embryonic development and in adult osteoblasts. Despite consistent expression in cells of the osteogenic lineage, SCL protein is not required for bone specification of embryonic stem cells. In transgenic mice, the SCL +19 core enhancer directed reporter gene expression to vascular smooth muscle and bone in addition to blood and endothelium. A 644-bp fragment containing the SCL +19 core enhancer was active in both blood and bone cell lines and was bound in vivo by a common array of Ets and GATA transcription factors. Taken together with the recent observation that a common progenitor can give rise to blood and bone cells, our results suggest that the SCL +19 enhancer targets a mesodermal progenitor capable of generating hematopoietic, vascular, and osteoblastic progeny.


2021 ◽  
Author(s):  
Deepika Puri ◽  
Birgit Koschorz ◽  
Bettina Engist ◽  
Megumi Onishi-Seebacher ◽  
Devon Ryan ◽  
...  

Repeat element transcription plays a vital role in early embryonic development. Expression of repeats such as MERVL characterises mouse embryos at the 2-cell stage, and defines a 2-cell-like cell (2CLC) population in a mouse embryonic stem cell culture. Repeat element sequences contain binding sites for numerous transcription factors. We identify the forkhead domain transcription factor FOXD3 as a regulator of repeat element transcription in mouse embryonic stem cells. FOXD3 binds to and recruits the histone methyltransferase SUV39H1 to MERVL and major satellite repeats, consequentially repressing the transcription of these repeats by the establishment of the H3K9me3 heterochromatin modification. Notably, depletion of FOXD3 leads to the de-repression of MERVL and major satellite repeats as well as a subset of genes expressed in the 2-cell state, shifting the balance between the stem cell and 2 cell-like population in culture. Thus, FOXD3 acts as a negative regulator of repeat transcription, ascribing a novel function to this transcription factor.


2021 ◽  
Vol 22 (9) ◽  
pp. 5011
Author(s):  
Daehwan Kim ◽  
Sangho Roh

Stem cell research is essential not only for the research and treatment of human diseases, but also for the genetic preservation and improvement of animals. Since embryonic stem cells (ESCs) were established in mice, substantial efforts have been made to establish true ESCs in many species. Although various culture conditions were used to establish ESCs in cattle, the capturing of true bovine ESCs (bESCs) has not been achieved. In this review, the difficulty of establishing bESCs with various culture conditions is described, and the characteristics of proprietary induced pluripotent stem cells and extended pluripotent stem cells are introduced. We conclude with a suggestion of a strategy for establishing true bESCs.


2010 ◽  
Vol 289 (2) ◽  
pp. 208-216 ◽  
Author(s):  
Shaker A. Mousa ◽  
Thangirala Sudha ◽  
Evgeny Dyskin ◽  
Usawadee Dier ◽  
Christine Gallati ◽  
...  

1994 ◽  
Vol 14 (5) ◽  
pp. 3108-3114
Author(s):  
M H Baron ◽  
S M Farrington

The zinc finger transcription factor GATA-1 is a major regulator of gene expression in erythroid, megakaryocyte, and mast cell lineages. GATA-1 binds to WGATAR consensus motifs in the regulatory regions of virtually all erythroid cell-specific genes. Analyses with cultured cells and cell-free systems have provided strong evidence that GATA-1 is involved in control of globin gene expression during erythroid differentiation. Targeted mutagenesis of the GATA-1 gene in embryonic stem cells has demonstrated its requirement in normal erythroid development. Efficient rescue of the defect requires an intact GATA element in the distal promoter, suggesting autoregulatory control of GATA-1 transcription. To examine whether GATA-1 expression involves additional regulatory factors or is maintained entirely by an autoregulatory loop, we have used a transient heterokaryon system to test the ability of erythroid factors to activate the GATA-1 gene in nonerythroid nuclei. We show here that proerythroblasts and mature erythroid cells contain a diffusible activity (TAG) capable of transcriptional activation of GATA-1 and that this activity decreases during the terminal differentiation of erythroid cells. Nuclei from GATA-1- mutant embryonic stem cells can still be reprogrammed to express their globin genes in erythroid heterokaryons, indicating that de novo induction of GATA-1 is not required for globin gene activation following cell fusion.


1989 ◽  
Vol 9 (10) ◽  
pp. 4563-4567
Author(s):  
T H Vu ◽  
G R Martin ◽  
P Lee ◽  
D Mark ◽  
A Wang ◽  
...  

Embryonal carcinoma and embryonic stem cells expressed a novel form of platelet-derived growth factor receptor mRNA which was approximately 1,100 base pairs shorter than the 5.3-kilobase (kb) transcript expressed in fibroblasts and other cell types. The 4.2-kb stem cell transcript was initiated within the genomic region immediately upstream of exon 6 of the 5.3-kb transcript and therefore lacked the first five exons, which encode much of the extracellular domain of the receptor expressed in fibroblasts. In stem cells, the short form was predominant, although both forms were present at low levels. Following differentiation in vitro, expression levels of the long form increased dramatically. These findings suggest that during early embryogenesis, a stem cell-specific promoter is used in a stage- and cell type-specific manner to express a form of the platelet-derived growth factor receptor that lacks much of the extracellular domain and may function independently of ligand.


2020 ◽  
Vol 133 (20) ◽  
pp. jcs255166

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Federico Pecori is first author on ‘Mucin-type O-glycosylation controls pluripotency in mouse embryonic stem cells via Wnt receptor endocytosis’, published in JCS. Federico is a PhD student in the lab of Shoko Nishihara at the Laboratory of Cell Biology, Department of Bioinformatics, Soka University, Tokyo, Japan, where he is interested in the mechanisms regulating stem cell identity.


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