Biomedical subjects

Yalin Guo

Publications and source records attributed to Yalin Guo.

3 recordsLinked to original sources

PubMed2003

Side-population cells from different precursor compartments.

The rapid efflux of the fluorescent DNA-binding dye Hoechst 33342 identifies a rare, so-called side population (SP), which rapidly expels the dye, can reconstitute the bone marrow (BM) of lethally irradiated mice, and has proven negative for most lineage markers including CD34. Because SP cells from human cell sources, such as mobilized peripheral blood [apheresis products (AP)], cord blood (CB), or BM have not been extensively characterized to date, we sought to analyze SP cells from various cell sources. We detected murine SP cells with a median frequency of 0.04% (n = 23) and a 52-fold colony-forming units (CFU) increase compared to unsorted cells (p = 0.028). The median frequency of human SP cells was 0.02% (n = 90), with highest numbers in donor AP, and lower in CB and BM. Human SP cells were mostly CD34(-) and lineage marker-negative. These showed no enrichment in CFU before expansion; however, they displayed a CFU increase after 5-7 days of cytokine-supported suspension culture (10.7-fold at day 5, 7.2-fold at day 7; n = 17) that was significant compared to both input (day 0) SP and to non-SP cells before and after expansion (p < 0.05). SP cells demonstrated a significant long-term culture-initiating cell (LTC-IC) increase of 167-fold (n = 17) as compared to non-SP cells (p = 0.002), with the highest numbers from AP specimens. We conclude that human primitive hematopoietic cells can be isolated via Hoechst staining and that SP cells of various human sources show substantial differences and represent a rare CD34(-) population with stem cell potential.

Animals↗

PubMed2003

CD34- hematopoietic stem cells: current concepts and controversies.

Recent data have suggested that human CD34(-) hematopoietic stem cells (HSCs) exist, challenging the concept that HSCs necessarily and exclusively express the CD34 antigen. In mice, quiescent HSCs have been shown to be mostly CD34(-), but as a consequence of 5-fluorouracil treatment or cytokine stimulation, differentiate into CD34(+) cells. Of particular interest is a novel, specific marker to identify HSCs, namely the Hoechst dye efflux property, with which a distinct side population (SP) is identified. These SP cells are mostly CD34(-), highly enriched for long-term repopulating cells, and durably engraft in sublethally irradiated non-obese diabetic/severe combined immunodeficient mice. Using a semiquantitative reverse transcription-polymerase chain reaction, one of the ATP-binding cassette (ABC) transporters, the breast cancer resistance protein (Bcrp) or ABC transporter G2 (ABCG2), was found to be highly expressed in SP cells as well as other primitive HSCs and to sharply drop with hematopoietic differentiation. Enforced expression of the ABCG2 cDNA resulted in a robust SP phenotype and a reduction in hematopoietic maturation. These data suggest that the Bcrp/ABCG2 gene contributes importantly to the generation of the SP phenotype, which allows for the selection of immature, pluripotent HSCs. The isolation of Bcrp/ABCG2(+) cells appears to be an attractive tool to analyze and characterize HSCs, and may eventually allow for the purification of these cells for clinical purposes. In this review, current concepts on murine and human CD34(-) HSCs and their relationship with CD34(+) HSCs are discussed.

Animals↗

PubMed2002

Telomere maintenance in human B lymphocytes.

Telomere shortening has been causally linked to replicative senescence in human cells. To characterize telomere-length heterogeneity in peripheral blood cells of normal individuals, we analysed the mean length of telomeric repeat sequences in subpopulations of peripheral blood leucocytes, using fluorescence in situ hybridization and flow cytometry (flow-FISH). Although the telomere length of most haematopoietic subsets was within the same range, the mean telomere length was found to be 15% higher in B compared with T lymphocytes in adult peripheral blood. Whereas telomere loss with ageing corresponded to 33 base pairs (bp) per year in T cells, telomere shortening was slower in B cells, corresponding to 15 bp per year. Separation of adult B-lymphocyte subpopulations based on CD27 expression revealed that telomere length was almost 2 kb longer in CD19+CD27+ (memory) compared with CD19+CD27- (naive) cells. Furthermore, peripheral blood B cells were activated in vitro. Whereas B-cell activation with Staphylococcus aureus Cowan strain (SAC) did not increase telomere length, a striking telomere elongation was observed when cells were stimulated with SAC and interleukin 2 to induce plasma cell differentiation. Our observations support the concept that telomere dynamics in B cells are distinct from other haematopoietic cell lineages and that telomere elongation may play an essential role in the generation of long-term B memory cells.

Adolescent↗