Article ID Journal Published Year Pages File Type
2078102 Cell Stem Cell 2010 11 Pages PDF
Abstract

SummarySustained blood cell production depends on divisions by hematopoietic stem cells (HSCs) that yield both differentiating progeny as well as new HSCs via self-renewal. Differentiating progeny remain capable of self-renewal, but only HSCs sustain self-renewal through successive divisions securely enough to maintain clones that persist life-long. Until recently, the first identified next stage consisted of “short-term” reconstituting cells able to sustain clones of differentiating cells for only 4–6 weeks. Here we expand evidence for a numerically dominant “intermediate-term” multipotent HSC stage in mice whose clones persist for 6–8 months before becoming extinct and that are separable from both short-term as well as permanently reconstituting “long-term” HSCs. The findings suggest that the first step in stem cell differentiation consists not in loss of initial capacity for serial self-renewal divisions, but rather in loss of mechanisms that stabilize self-renewing behavior throughout successive future stem cell divisions.

► Individual purified HSCs show sustained or transient reconstitution ► Intermediate-term hematopoietic stem cells (ITRCs) have prolonged but limited lifespan ► ITRCs outnumber long-term cells in highly purified fractions ► Intermediate-term cells enriched based on integrin α2 expression

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