Hematopoiesis: An Evolving Paradigm for Stem Cell Biology

Orkin, Stuart H.; Zon, Leonard I.

doi:10.1016/j.cell.2008.01.025

Cited by 2,164 publications

(2,049 citation statements)

References 112 publications

(121 reference statements)

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“…In the mammalian embryo, the first site of hematopoiesis occurs in the extra-embryonic YS blood islands at around embryonic age 7.5 (E7.5), which is called primitive hematopoiesis (Orkin and Zon, 2008). The main function of the primitive hematopoiesis is to generate primitive red blood cells and macrophages (Lichanska and Hume, 2000;Lichanska et al, 1999).…”

Section: Origin Of Microgliamentioning

confidence: 99%

Regulation of microglia development and homeostasis

Greter

Mérad

2012

Glia

118

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Microglia represent the resident macrophages of the central nervous system (CNS) and account for 10% of the adult glial cell population in the normal brain. Although microglial cells are thought to contribute to most pathological conditions including CNS infections, neuroinflammatory lesions, brain tumors, and neurodegenerative diseases, their exact role in CNS development, homeostasis, and disease remains poorly understood. In contrast to most macrophage populations, microglia survive high-dose ionizing radiation and maintain themselves locally and independently of circulating precursors in the steady state. However, controversies remain on the origin of microglia in the brain and whether they could potentially be repopulated by circulating myeloid precursors after brain injury. Microgliatargeted therapies through the use of genetically modified circulating hematopoietic cells proved to be a promising therapeutic strategy for the treatment of brain diseases. It is thus of great importance to understand the contribution and developmental cues of circulating myeloid cells as potential microglia progenitors to the adult pool of microglia in the steady state and under inflammatory conditions. V

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Section: Origin Of Microgliamentioning

confidence: 99%

Regulation of microglia development and homeostasis

Greter

Mérad

2012

Glia

118

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“…Members of the 'signal lymphocyte activation molecule' (SLAM) family help define murine HSCs; adding CD150 + CD48 − to the Sca-1 + Lin − c-kit + selection criteria greatly improved long-term multilineage reconstitution in irradiated mice [79]. Recent advances in HSC self-renewal have been reviewed elsewhere [80,81].…”

Section: Bone Marrowmentioning

confidence: 99%

Attributes of adult stem cells

Alison

Islam

2008

The Journal of Pathology

153

115

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While cultured embryonic stem (ES) cells can be harvested in abundance and appear to be the most versatile of cells for regenerative medicine, adult stem cells also hold promise, but the identity and subsequent isolation of these comparatively rare cells remains problematic in most tissues, perhaps with the notable exception of the bone marrow. The ability to continuously self-renew and produce the differentiated progeny of the tissue of their location are their defining properties. Identifying surface molecules (markers) that would aid in stem cell isolation is a major goal. Considerable overlap exists between different putative organspecific stem cells in their repertoire of gene expression, often related to self-renewal, cell survival and cell adhesion. More robust tests of 'stemness' are now being employed, using lineage-specific genetic marking and tracking to show production of long-lived clones and multipotentiality in vivo. Moreover, the characterization of normal stem cells in specific tissues may provide a dividend for the treatment of cancer. The successful treatment of neoplastic disease may well require the specific targeting of neoplastic stem cells, cells that may well have many of the characteristics of their normal counterparts.

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“…Hematopoietic stem cells (HSCs) are a rare self-renewing bone marrow (BM) cell population that maintains blood and the immune system throughout life [1,2]. Under nonstress conditions, young adult murine HSCs lack expression of several cell surface lineage markers normally found on differentiating or mature blood cells while displaying high levels of Sca-1 and c-Kit.…”

Section: Introductionmentioning

confidence: 99%

Phenotypic and Functional Changes Induced in Hematopoietic Stem/Progenitor Cells After Gamma-Ray Radiation Exposure

et al. 2009

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Ionizing radiation (IR) exposure causes rapid and acute bone marrow (BM) suppression that is reversible for nonlethal doses. Evidence is accumulating that IR can also provoke long-lasting residual hematopoietic injury. To better understand these effects, we analyzed phenotypic and functional changes in the stem/progenitor compartment of irradiated mice over a 10-week period. We found that hematopoietic stem cells (HSCs) identified by their repopulating ability continued to segregate within the Hoechst dye excluding ''side population (SP)'' early after IR exposure. However, transient phenotypic changes were observed within this cell population: Sca-1 (S) and c-Kit (K) expression levels were increased and severely reduced, respectively, with a concurrent increase in the proportion of SP SK cells positive for established indicators of the presence of HSCs: CD150 and CD105. Ten weeks after IR exposure, expression of Sca-1 and c-Kit at the SP cell surface returned to control levels, and BM cellularity of irradiated mice was restored. However, the c-Kit 1 Sca-1 1 Lin 2/low (KSL) stem/progenitor compartment displayed major phenotypic modifications, including an increase and a severe decrease in the frequencies of CD150 1 Flk2 2 and CD150 2 Flk2 1 cells, respectively. CD150 1 KSL cells also showed impaired reconstituting ability, an increased tendency to apoptosis, and accrued DNA damage. Finally, 15 weeks after exposure, irradiated mice, but not agematched controls, allowed engraftment and significant hematopoietic contribution from transplanted congenic HSCs without additional host conditioning. These results provide novel insight in our understanding of immediate and delayed IR-induced hematopoietic injury and highlight similarities between HSCs of young irradiated and old mice.

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Hematopoiesis: An Evolving Paradigm for Stem Cell Biology

Cited by 2,164 publications

References 112 publications

Regulation of microglia development and homeostasis

Regulation of microglia development and homeostasis

Attributes of adult stem cells

Phenotypic and Functional Changes Induced in Hematopoietic Stem/Progenitor Cells After Gamma-Ray Radiation Exposure

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