Posted on 05/22/2008 10:27:42 PM PDT by neverdem
Bone marrow stem cells waver before committing to develop into specialized blood cellsIf two roads diverged in a yellow wood, random fluctuations would influence which road stem cells traveled.
A new understanding of how stem cells choose among their possible fates could aid development of stem cell therapies for diseases, scientists say. A type of adult stem cell in bone marrow can develop along one of two paths: either the red or white blood cell lineages. Scientists have wondered why some bone marrow cells follow one path while other, seemingly identical cells go down the other.
New research shows that these bone marrow stem cells are not in fact a single, sharply defined type of cell, but rather have a blurry range of traits. Gene activity determines a cell’s biochemical traits, and for these stem cells, this genetic activity varies over a period of days. Each stem cell slowly “wanders” within the range, sometimes producing proteins that prime the cell for the red blood cell pathway, other times prepping the cell for the white blood cell option.
So a large group of stem cells will always contain a variety of cells covering this complete range of traits, distributed in a familiar bell curve.
“It’s like a cloud of mosquitoes,” explains lead scientist Sui Huang of Harvard Medical School in Boston. The varied cells “kind of stay together, though each one of them is moving around” within the range of possible traits. When cues in the cells’ surroundings trigger the cells to choose a fate, each cell will follow the path that it happens to be primed for at that moment, Huang and his colleagues report May 22 in Nature.
The researchers isolated three subgroups of mouse bone marrow stem cells according to where the cells fell within the bell curve...
(Excerpt) Read more at sciencenews.org ...
Phenotypic cell-to-cell variability within clonal populations may be a manifestation of 'gene expression noise'1, 2, 3, 4, 5, 6, or it may reflect stable phenotypic variants7. Such 'non-genetic cell individuality'7 can arise from the slow fluctuations of protein levels8 in mammalian cells. These fluctuations produce persistent cell individuality, thereby rendering a clonal population heterogeneous. However, it remains unknown whether this heterogeneity may account for the stochasticity of cell fate decisions in stem cells. Here we show that in clonal populations of mouse haematopoietic progenitor cells, spontaneous 'outlier' cells with either extremely high or low expression levels of the stem cell marker Sca-1 (also known as Ly6a; ref. 9) reconstitute the parental distribution of Sca-1 but do so only after more than one week. This slow relaxation is described by a gaussian mixture model that incorporates noise-driven transitions between discrete subpopulations, suggesting hidden multi-stability within one cell type. Despite clonality, the Sca-1 outliers had distinct transcriptomes. Although their unique gene expression profiles eventually reverted to that of the median cells, revealing an attractor state, they lasted long enough to confer a greatly different proclivity for choosing either the erythroid or the myeloid lineage. Preference in lineage choice was associated with increased expression of lineage-specific transcription factors, such as a >200-fold increase in Gata1 (ref. 10) among the erythroid-prone cells, or a >15-fold increased PU.1 (Sfpi1) (ref. 11) expression among myeloid-prone cells. Thus, clonal heterogeneity of gene expression level is not due to independent noise in the expression of individual genes, but reflects metastable states of a slowly fluctuating transcriptome that is distinct in individual cells and may govern the reversible, stochastic priming of multipotent progenitor cells in cell fate decision.
haematopoietic progenitor cells = red and white blood cell precursors
erythroid or the myeloid lineage = red or white blood cells, the latter not including lymphocytes
stem cell ping
stem cell science ping
Fascinating and it makes sense that cells would wait a short period of time to differentiate. Esp considering the various mechanisms are at work in the body to combat whichever immunological threat is not being eliminated. Otherwise, I suppose the body would be overwhelmed by RBC or WBC production for some temporary problem that is being rectified, in part, by other body systems.
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