Emergence of definitive hematopoiesis in Myb-null mouse embryos

2017 ◽  
Vol 53 ◽  
pp. S31
Author(s):  
James Palis ◽  
Jenna Frame ◽  
Emanuele Azzoni ◽  
Anne Koniski ◽  
Jacquelyn Lillis ◽  
...  
Keyword(s):  
Mouse Embryos ◽  
Null Mouse ◽  
Definitive Hematopoiesis

scholarly journals Redundant mechanisms driven independently by RUNX1 and GATA2 for hematopoietic development

2021 ◽  
Author(s):  
Erica Bresciani ◽  
Blake Carrington ◽  
Kai Yu ◽  
Erika Kim ◽  
Tao Zhen ◽  
...  
Keyword(s):  
Blood Cells ◽  
Mouse Embryos ◽  
Null Mouse ◽  
Compensatory Mechanism ◽  
Hematopoietic Stem ◽  
Hematopoietic Development ◽  
Genetic Inactivation ◽  
Signature Genes ◽  
Single Cell Rna Sequencing ◽  
Definitive Hematopoiesis

RUNX1 is essential for the generation of hematopoietic stem cells (HSCs). Runx1 null mouse embryos lack definitive hematopoiesis and die in mid-gestation. However, even though zebrafish embryos with a runx1 W84X mutation have defects in early definitive hematopoiesis, some runx1W84X/W84X embryos can develop to fertile adults with blood cells of multi-lineages, raising the possibility that HSCs can emerge without RUNX1. Here, using three new zebrafish runx1-/- lines we uncovered the compensatory mechanism for runx1-independent hematopoiesis. We show that, in the absence of a functional runx1, a cd41-GFP+ population of hematopoietic precursors still emerge from the hemogenic endothelium and can colonize the hematopoietic tissues of the mutant embryos. Single-cell RNA sequencing of the cd41-GFP+ cells identified a set of runx1-/--specific signature genes during hematopoiesis. Significantly, gata2b, which normally acts upstream of runx1 for the generation of HSCs, was increased in the cd41-GFP+ cells in runx1- /- embryos. Interestingly, genetic inactivation of both gata2b and its paralog, gata2a, did not affect hematopoiesis. However, knocking out runx1 and any three of the four alleles of gata2a and gata2b abolished definitive hematopoiesis. Gata2 expression was also upregulated in hematopoietic cells in Runx1-/- mice, suggesting the compensatory mechanism is conserved. Our findings indicate that RUNX1 and GATA2 serve redundant roles for HSC production, acting as safeguard for each other.

scholarly journals Redundant mechanisms driven independently by RUNX1 and GATA2 for hematopoietic development

2021 ◽  
Author(s):  
Erica Bresciani ◽  
Blake Carrington ◽  
Kai Yu ◽  
Erika Mijin Kwon Kim ◽  
Tao Zhen ◽  
...  
Keyword(s):  
Blood Cells ◽  
Mouse Embryos ◽  
Null Mouse ◽  
Compensatory Mechanism ◽  
Hematopoietic Stem ◽  
Hematopoietic Development ◽  
Genetic Inactivation ◽  
Signature Genes ◽  
Single Cell Rna Sequencing ◽  
Definitive Hematopoiesis

RUNX1 is essential for the generation of hematopoietic stem cells (HSCs). Runx1 null mouse embryos lack definitive hematopoiesis and die in mid-gestation. However, even though zebrafish embryos with a runx1 W84X mutation have defects in early definitive hematopoiesis, some runx1W84X/W84X embryos can develop to fertile adults with blood cells of multi-lineages, raising the possibility that HSCs can emerge without RUNX1. Here, using three new zebrafish runx1-/- lines we uncovered the compensatory mechanism for runx1-independent hematopoiesis. We show that, in the absence of a functional runx1, a cd41-GFP+ population of hematopoietic precursors still emerge from the hemogenic endothelium and can colonize the hematopoietic tissues of the mutant embryos. Single-cell RNA sequencing of the cd41-GFP+ cells identified a set of runx1-/--specific signature genes during hematopoiesis. Significantly, gata2b, which normally acts upstream of runx1 for the generation of HSCs, was increased in the cd41-GFP+ cells in runx1- /- embryos. Interestingly, genetic inactivation of both gata2b and its paralog, gata2a, did not affect hematopoiesis. However, knocking out runx1 and any three of the four alleles of gata2a and gata2b abolished definitive hematopoiesis. Gata2 expression was also upregulated in hematopoietic cells in Runx1-/- mice, suggesting the compensatory mechanism is conserved. Our findings indicate that RUNX1 and GATA2 serve redundant roles for HSC production, acting as each other's safeguard.

scholarly journals Conditional knock-out reveals that zygotic vezatin-null mouse embryos die at implantation

2007 ◽  
Vol 124 (6) ◽  
pp. 449-462 ◽  
Author(s):  
Vincent Hyenne ◽  
Céline Souilhol ◽  
Michel Cohen-Tannoudji ◽  
Silvia Cereghini ◽  
Christine Petit ◽  
...  
Keyword(s):  
Mouse Embryos ◽  
Null Mouse ◽  
Knock Out

scholarly journals Gene expression profiles of Bapx1 expressing FACS sorted cells from wildtype and Bapx1-EGFP null mouse embryos

Genomics Data ◽  
2015 ◽  
Vol 5 ◽  
pp. 103-105 ◽  
Author(s):  
Sumantra Chatterjee ◽  
V. Sivakamasundari ◽  
Petra Kraus ◽  
Sook Peng Yap ◽  
Vibhor Kumar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Mouse Embryos ◽  
Null Mouse

scholarly journals Psg22 null mouse embryos develop normally under normoxic and hypoxic conditions of pregnancy     

Matters ◽  
2016 ◽  
Author(s):  
John Williams ◽  
Tania Bezak ◽  
Mrinmoy Das ◽  
Zhenfei Ning ◽  
Eric Lucking ◽  
...  
Keyword(s):  
Mouse Embryos ◽  
Null Mouse ◽  
Hypoxic Conditions

Analysis of Hornozygous TGF?1 Null Mouse Embryos Demonstrates Defects in Yolk Sac. Vasculogenesis and Hematopoiesis

1995 ◽  
Vol 752 (1 Cardiac Growt) ◽  
pp. 300-308 ◽  
Author(s):  
JULIE S. MARTIN ◽  
MARION C. DICKSON ◽  
FRANCES M. COUSINS ◽  
ASHOK B. KULKARNI ◽  
STEFAN KARLSSON ◽  
...  
Keyword(s):  
Yolk Sac ◽  
Mouse Embryos ◽  
Null Mouse

scholarly journals Tgif1 and Tgif2 Repress Expression of the RabGAP Evi5l

2016 ◽  
Vol 37 (5) ◽  
Author(s):  
Anoush E. Anderson ◽  
Kenichiro Taniguchi ◽  
Yi Hao ◽  
Tiffany A. Melhuish ◽  
Anant Shah ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Retinal Pigment Epithelial Cell ◽  
Retinal Pigment ◽  
Transcriptional Response ◽  
Mouse Embryos ◽  
Epithelial Cell Line ◽  
Null Mouse ◽  
Altered Expression ◽  
Partial Restoration ◽  
Shh Pathway

ABSTRACT Mouse embryos conditionally lacking Tgif1 and Tgif2 have holoprosencephaly and defects in left-right asymmetry. To identify pathways affected by loss of Tgif function during embryogenesis, we performed transcriptome profiling on whole mouse embryos. Among the genes with altered expression in embryos lacking Tgifs were a number with links to cilium function. One of these, Evi5l, encodes a RabGAP that is known to block the formation of cilia when overexpressed. Evi5l expression is increased in Tgif1; Tgif2-null embryos and in double-null mouse embryo fibroblasts (MEFs). Knockdown of Tgifs in a human retinal pigment epithelial cell line also increased EVI5L expression. We show that TGIF1 binds to a conserved consensus TGIF site 5′ of the human and mouse Evi5l genes and represses Evi5l expression. In primary MEFs lacking both Tgifs, the number of cells with primary cilia was significantly decreased, and we observed a reduction in the transcriptional response to Shh pathway activation. Reducing Evi5l expression in MEFs lacking Tgifs resulted in a partial restoration of cilium numbers and in the transcriptional response to activation of the Shh pathway. In summary, this work shows that Tgifs regulate ciliogenesis and suggests that Evi5l mediates at least part of this effect.

scholarly journals Transketolase Haploinsufficiency Reduces Adipose Tissue and Female Fertility in Mice

2002 ◽  
Vol 22 (17) ◽  
pp. 6142-6147 ◽  
Author(s):  
Zheng-Ping Xu ◽  
Eric F. Wawrousek ◽  
Joram Piatigorsky
Keyword(s):  
Adipose Tissue ◽  
Metabolic Pathways ◽  
Well Being ◽  
Threshold Level ◽  
Mouse Embryos ◽  
Null Mouse ◽  
Wild Type ◽  
Small Female ◽  
Female Ratio ◽  
Male Female Ratio

ABSTRACT Transketolase (TKT) is a ubiquitous enzyme used in multiple metabolic pathways. We show here by gene targeting that TKT-null mouse embryos are not viable and that disruption of one TKT allele can cause growth retardation (≈35%) and preferential reduction of adipose tissue (≈77%). Other TKT+/− tissues had moderate (≈33%; liver, gonads) or relatively little (≈7 to 18%; eye, kidney, heart, brain) reductions in mass. These mice expressed a normal level of growth hormone and reduced leptin levels. No phenotype was observed in the TKT+/− cornea, where TKT is especially abundant in wild-type mice. The small female TKT+/− mice mated infrequently and had few progeny (with a male/female ratio of 1.4:1) when pregnant. Thus, TKT in normal mice appears to be carefully balanced at a threshold level for well-being. Our data suggest that TKT deficiency may have clinical significance in humans and raise the possibility that obesity may be treated by partial inhibition of TKT in adipose tissue.

scholarly journals Programmed cell death by default in embryonic cells, fibroblasts, and cancer cells.

1995 ◽  
Vol 6 (11) ◽  
pp. 1443-1458 ◽  
Author(s):  
Y Ishizaki ◽  
L Cheng ◽  
A W Mudge ◽  
M C Raff
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Cancer Cells ◽  
Cell Line ◽  
Mammalian Cells ◽  
Cell Types ◽  
Mouse Embryos ◽  
Leukemia Cell Line ◽  
Null Mouse ◽  
Human Leukemia

We recently proposed that most mammalian cells constitutively express all of the proteins required to undergo programmed cell death (PCD) and undergo PCD unless continuously signaled by other cells not to. Although some cells have been shown to work this way, the vast majority of cell types remain to be tested. Here we tested purified fibroblasts isolated from developing or adult rat sciatic nerve, a mixture of cell types isolated from normal or p53-null mouse embryos, an immortalized rat fibroblast cell line, and a number of cancer cell lines. We found the following: 1) All of these cells undergo PCD when cultured at low cell density in the absence of serum and exogenous signaling molecules but can be rescued by serum or specific growth factors, suggesting that they need extracellular signals to avoid PCD. (2) The mixed cell types dissociated from normal mouse embryos can only support one another's survival in culture if they are in aggregates, suggesting that cell survival in embryos may depend on short-range signals. (3) Some cancer cells secrete factors that support their own survival. (4) The survival requirements of a human leukemia cell line change when the cells differentiate. (5) All of the cells studied can undergo PCD in the presence of cycloheximide, suggesting that they constitutively express all of the protein components required to execute the death program.

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