Stem cells: the new “model organism”

Human tissue culture cells have long been a staple of molecular and cell biology research. However, although these cells are derived from humans, they have often lost considerable aspects of natural physiological function. Here we argue that combined advances in genome editing, stem cell production, and organoid derivation from stem cells represent a revolution in cell biology. These advances have important ramifications for the study of basic cell biology mechanisms, as well as for the ways in which discoveries in mechanisms are translated into understanding of disease.

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The human CD34 hematopoietic stem cell antigen promoter and a 3' enhancer direct hematopoietic expression in tissue culture

Blood ◽

10.1182/blood.v80.12.3051.3051 ◽

1992 ◽

Vol 80 (12) ◽

pp. 3051-3059 ◽

Cited By ~ 26

Author(s):

TC Burn ◽

AB Satterthwaite ◽

DG Tenen

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Tissue Culture ◽

Stem Cell ◽

Transcription Factors ◽

Progenitor Cell ◽

Hematopoietic Stem ◽

Culture Cells ◽

Human Cd34 ◽

Tissue Culture Cells

Abstract The human CD34 hematopoietic stem cell antigen is a highly glycosylated type 1 membrane protein of unknown function. CD34 is expressed on 1% to 4% of bone marrow cells, including pluripotent stem cells and committed progenitors of each hematopoietic lineage. CD34 has also been shown to be expressed on the small vessel endothelium of a variety of tissues and on a subset of bone marrow stromal cells. We have chosen to use the human CD34 gene as model to examine the transcription factors and cis-elements required for stem cell/progenitor cell-specific gene regulation. We show here that the CD34 gene is transcriptionally regulated in tissue culture cells. Using a luciferase reporter gene, we have isolated and characterized an active CD34 promoter. A CD34- luciferase construct, containing 4.5 kb of 5′ flanking DNA from a CD34 genomic clone, was 30-fold more active in CD34+ tissue culture cells than in HeLa cells. Sequences from the 3′ end of the CD34 gene were shown to have enhancing activity in CD34+ T-lymphoblastic RPMI-8402 cells and not in CD34- U937 cells or in nonhematopoietic HeLa cells. We also show that a cytidine-guanosine island in the 5′ end of the CD34 gene is heavily methylated in two CD34- hematopoietic cell lines and demethylated in two CD34+ cell lines. Analysis of the CD34 promoter should result in the identification of stem cell/progenitor cell- specific transcription factors and should provide a means to direct the expression of heterologous genes in hematopoietic stem cells and progenitors.

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The human CD34 hematopoietic stem cell antigen promoter and a 3' enhancer direct hematopoietic expression in tissue culture

Blood ◽

10.1182/blood.v80.12.3051.bloodjournal80123051 ◽

1992 ◽

Vol 80 (12) ◽

pp. 3051-3059 ◽

Cited By ~ 1

Author(s):

TC Burn ◽

AB Satterthwaite ◽

DG Tenen

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Tissue Culture ◽

Stem Cell ◽

Transcription Factors ◽

Progenitor Cell ◽

Hematopoietic Stem ◽

Culture Cells ◽

Human Cd34 ◽

Tissue Culture Cells

The human CD34 hematopoietic stem cell antigen is a highly glycosylated type 1 membrane protein of unknown function. CD34 is expressed on 1% to 4% of bone marrow cells, including pluripotent stem cells and committed progenitors of each hematopoietic lineage. CD34 has also been shown to be expressed on the small vessel endothelium of a variety of tissues and on a subset of bone marrow stromal cells. We have chosen to use the human CD34 gene as model to examine the transcription factors and cis-elements required for stem cell/progenitor cell-specific gene regulation. We show here that the CD34 gene is transcriptionally regulated in tissue culture cells. Using a luciferase reporter gene, we have isolated and characterized an active CD34 promoter. A CD34- luciferase construct, containing 4.5 kb of 5′ flanking DNA from a CD34 genomic clone, was 30-fold more active in CD34+ tissue culture cells than in HeLa cells. Sequences from the 3′ end of the CD34 gene were shown to have enhancing activity in CD34+ T-lymphoblastic RPMI-8402 cells and not in CD34- U937 cells or in nonhematopoietic HeLa cells. We also show that a cytidine-guanosine island in the 5′ end of the CD34 gene is heavily methylated in two CD34- hematopoietic cell lines and demethylated in two CD34+ cell lines. Analysis of the CD34 promoter should result in the identification of stem cell/progenitor cell- specific transcription factors and should provide a means to direct the expression of heterologous genes in hematopoietic stem cells and progenitors.

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Inactivating Gene Expression with Antisense Modified Oligonucleotides

Acta Naturae ◽

10.32607/actanaturae.11522 ◽

2021 ◽

Vol 13 (3) ◽

pp. 101-105

Author(s):

Sidney Altman ◽

Carlos Angele-Martinez

Keyword(s):

Gene Expression ◽

Tissue Culture ◽

Plasmodium Falciparum ◽

Human Tissue ◽

Target Gene ◽

Modified Oligonucleotides ◽

Modified Nucleotides ◽

Culture Cells ◽

Tissue Culture Cells

Modified nucleotides, including phosphoramidates and mesyl nucleotides, are very effective in inactivating gene expression in bacteria. Gyr A is the target gene in several organisms, including Plasmodium falciparum. Antisense reactions with bacteria infecting citrus plants are promising but incomplete. Human tissue culture cells assayed with a different target are also susceptible to the presence of mesyl oligonucleotides.

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