Telomerase Activity in Candidate Stem Cells From Fetal Liver and Adult Bone Marrow
Open accessAbstract
Telomerase is a ribonucleoprotein polymerase that synthesizes telomeric repeats onto the 3′ ends of eukaryotic chromosomes. Activation of telomerase may prevent telomeric shortening and correlates with cell immortality in the germline and certain tumor cells. Candidate hematopoietic stem cells (HSC) from adult bone marrow express low levels of telomerase, which is upregulated with proliferation and/or differentiation. To address this issue, we stimulated purified candidate HSC from human adult bone marrow with stem cell factor (SCF), interleukin-3 (IL-3), and Flt3-ligand (FL). After 5 days in culture, activity was detected in total cell extracts from IL-3–, SCF + FL–, SCF + IL-3–, FL + IL-3–, and SCF + IL-3 + FL–stimulated cultures, but not from cells cultured in SCF or FL alone. Within the CD34+fraction of the cultured cells, significant activity was found in the CD34+CD71+ fraction. In addition, PKH26 staining confirmed that detectable telomerase activity was present in dividing PKH26lo cells, whereas nondividing PKH26hi cells were telomerase negative. Because in these experiments no distinction could be made between cycling “candidate” stem cells that had retained or had lost self-renewal properties, fetal liver cells with a CD34+CD38− phenotype, highly enriched for cycling stem cells, were also examined and found to express readily detectable levels of telomerase activity. Given the replication-dependent loss of telomeric DNA in hematopoietic cells, these observations suggest that the observed telomerase activity in candidate stem cells is either expressed in a minor subset of stem cells or, more likely, is not sufficient to prevent telomere shortening.
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Early studies found strong suppression of TERT expression and telomerase activity in human somatic tissues, but robust expression in germ cells and cancer cells.
“Early studies cataloging TERT expression and telomerase activity reported potent suppression in human somatic tissues, yet robust expression and activity in germ cells and cancer cells (48).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [48]
The vast majority of spontaneous human cancers express robust telomerase activity.
“the seminal observation that the vast majority of spontaneous human cancers express robust levels of telomerase activity (48).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [48]
In stem cell and progenitor cell compartments, TERT serves an important role in keeping telomeres sufficiently long and stable to prevent the adverse consequences of dysfunctional telomeres on cell viability and chromosomal stability.
“In stem cell and progenitor cell compartments3–5, TERT serves an important role in keeping telomeres sufficiently long and stable to prevent the adverse consequences of dysfunctional telomeres on cell viability and chromosomal stability6–8.”
From Conditional telomerase induction causes proliferation of hair follicle stem cells (2005) · cites this paper as [4]
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- Authors
- Yui, J., Chiu, C.-P., & Lansdorp, P. M.
- Affiliations
- BC Cancer Agency (CA)
- ORCID
- Lansdorp, Peter M.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 1998-05-01
- Volume
- 91
- Issue
- 9
- Pages
- 3255-3262
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W97711432
- Cited by
- 216
- References
- 51
- Citations by year
- 2024: 4 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 3 · 2016: 7 · 2015: 7 · 2014: 7 · 2013: 7 · 2012: 8
- FWCI
- 8.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r01gm056162-01)
- National Institute of General Medical Sciences (GM56162)
- National Institute of Allergy and Infectious Diseases (AI 29524)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- telomerase activity, hematopoietic stem cells, fetal liver, bone marrow, CD34+CD38- cells, stem cell factor, interleukin-3, Flt3 ligand, cell proliferation, telomere shortening, self-renewal
- MeSH terms
- Adult, Antigens, Differentiation, Bone Marrow Cells, Cell Differentiation, Cell Division, Hematopoietic Stem Cells, Humans, Liver, Membrane Glycoproteins, Membrane Proteins, NAD+ Nucleosidase, Antigens, CD, Antigens, CD34, Stem Cell Factor, Telomerase, ADP-ribosyl Cyclase, ADP-ribosyl Cyclase 1
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