Using divisional history to measure hematopoietic stem cell self-renewal and differentiation

Yan, Feng; Collector, Michael I.; Tyszko, Sara; Sharkis, Saul J.

doi:10.1016/s0301-472x(02)01012-3

Cited by 11 publications

(8 citation statements)

References 31 publications

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“…Previous attempts to investigate HSC proliferation history have been limited to assays that involve in vitro manipulation of donor cell populations for efficient labeling, or that require fixation to permit experimental readout [2], [3], [5], [8], [22]. Therefore, most existing experimental data for HSC quiescence has been correlative, resting on the phenotypic identity of HSCs rather than their functional capacities.…”

Section: Discussionmentioning

confidence: 99%

A Novel Assay to Trace Proliferation History In Vivo Reveals that Enhanced Divisional Kinetics Accompany Loss of Hematopoietic Stem Cell Self-Renewal

Nygren

Bryder

2008

PLoS ONE

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BackgroundThe maintenance of lifelong blood cell production ultimately rests on rare hematopoietic stem cells (HSCs) that reside in the bone marrow microenvironment. HSCs are traditionally viewed as mitotically quiescent relative to their committed progeny. However, traditional techniques for assessing proliferation activity in vivo, such as measurement of BrdU uptake, are incompatible with preservation of cellular viability. Previous studies of HSC proliferation kinetics in vivo have therefore precluded direct functional evaluation of multi-potency and self-renewal, the hallmark properties of HSCs.Methodology/Principal FindingsWe developed a non-invasive labeling technique that allowed us to identify and isolate candidate HSCs and early hematopoietic progenitor cells based on their differential in vivo proliferation kinetics. Such cells were functionally evaluated for their abilities to multi-lineage reconstitute myeloablated hosts.ConclusionsAlthough at least a few HSC divisions per se did not influence HSC function, enhanced kinetics of divisional activity in steady state preceded the phenotypic changes that accompanied loss of HSC self-renewal. Therefore, mitotic quiescence of HSCs, relative to their committed progeny, is key to maintain the unique functional and molecular properties of HSCs.

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Section: Discussionmentioning

confidence: 99%

A Novel Assay to Trace Proliferation History In Vivo Reveals that Enhanced Divisional Kinetics Accompany Loss of Hematopoietic Stem Cell Self-Renewal

Nygren

Bryder

2008

PLoS ONE

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“…7A), to test the timing of subsequent cell divisions. Because PKH26 is distributed proportionally among daughter cells following mitosis (29), it allows high-resolution cell division tracking.…”

Section: Actively Proliferating Lt-hscs Sustain a Prolonged Cell Cyclmentioning

confidence: 99%

Prolonged Cell Cycle Transit Is a Defining and Developmentally Conserved Hemopoietic Stem Cell Property

Nygren

Bryder

Jacobsen

2006

The Journal of Immunology

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Adult mouse hemopoietic stem cells (HSCs) are typically quiescent and enter and progress through the cell cycle rarely in steady-state bone marrow, but their rate of proliferation can be dramatically enhanced on demand. We have studied the cell cycle kinetics of HSCs in the developing fetal liver at a stage when they expand extensively. Despite that 100% of fetal liver HSCs divide within a 48-h period, their average cell cycle transit time (10.6 h) is twice that of their downstream progenitors, translating into a prolonged G1 transit and a period of relative quiescence (G0). In agreement with their prolonged G1 transit when compared with hemopoietic progenitors, competitive transplantation experiments demonstrate that fetal HSCs are highly enriched in G1 but also functional in S-G2-M. This observation combined with experimental data demonstrating that adult HSCs forced to expand ex vivo also sustain a uniquely prolonged cell cycle and G1 transit, demonstrate at least in part why purified HSCs at any state of development or condition are highly enriched in the G0-G1 phases of the cell cycle. We propose that a uniquely prolonged cell cycle transit is a defining stem cell property, likely to be critical for their maintenance and self-renewal throughout development.

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“…We and others have demonstrated that the membrane dye PKH26 could be exploited to assist in isolation of the quiescent or SDF. 16,[24][25][26] In continuation with this line of research, the CD34 ϩ /CD38 Ϫ cells were separated into an SDF and a fast-dividing fraction (FDF). Global gene expression profiles for these 2 populations…”

Section: Introductionmentioning

confidence: 99%

Molecular evidence for stem cell function of the slow-dividing fraction among human hematopoietic progenitor cells by genome-wide analysis

Wagner

Ansorge

Wirkner

et al. 2004

Blood

122

127

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Using divisional history to measure hematopoietic stem cell self-renewal and differentiation

Cited by 11 publications

References 31 publications

A Novel Assay to Trace Proliferation History In Vivo Reveals that Enhanced Divisional Kinetics Accompany Loss of Hematopoietic Stem Cell Self-Renewal

A Novel Assay to Trace Proliferation History In Vivo Reveals that Enhanced Divisional Kinetics Accompany Loss of Hematopoietic Stem Cell Self-Renewal

Prolonged Cell Cycle Transit Is a Defining and Developmentally Conserved Hemopoietic Stem Cell Property

Molecular evidence for stem cell function of the slow-dividing fraction among human hematopoietic progenitor cells by genome-wide analysis

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