Stem Cells Units of Development, Units of Regeneration, and Units in Evolution

  title={Stem Cells Units of Development, Units of Regeneration, and Units in Evolution},
  author={Irving L. Weissman},

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It is demonstrated that the helix-loop-helix (HLH) transcription factor Id2 (inhibitor of DNA binding/differentiation 2) acts as a molecular switch in development of Langerhans cells (LCs), the cutaneous contingent of dendritic cells (DCs), and of specific DC subsets and B cells.

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Comparison of differentiation potentials between individual pairs of daughter and granddaughter cells derived in vitro from single nmEM cells strongly suggest that lineage commitment takes place asymmetrically at the level of HSCs under the influence of external factors.

Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations.

This review is about the properties of various highly purified tissue-specific multipotent stem cells and purified oligolineage progenitors and contends that unless the stem or progenitor cells in question have been purified to near homogeneity, one cannot know whether their generation of expected or unexpected progeny is a property of a known cell type.

TISSUE-SPECIFIC STEM CELLS Maintenance of Undifferentiated State and Self-Renewal of Embryonic Neural Stem Cells by Polycomb Protein Ring 1 B

It is shown that neural stem/progenitor cell proliferation in vivo and in neurosphere assays is impaired, lacking Ring1B, and their selfrenewal and multipotential abilities, assessed as sphere formation and differentiation from single cells, are severely affected.

Direct isolation of human central nervous system stem cells.

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    Proceedings of the National Academy of Sciences of the United States of America
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Definitions and criteria for stem cells.

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The complexity of NSCs, neural patterning, and the formation of multiple populations of neurons, astrocytes, and oligodendrocyte warrant the need for intense studies to characterize these cells and to define the microenvironment that will be needed to support them in the diseased CNS.

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Some of the evidence for stem cell plasticity in rodents and man is reviewed, finding that appropriately differentiated cells are delivered deep within organs simply by injection of bone marrow cells, and should make us think differently about the way that organs regenerate and repair.

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The dynamics that regulate which and how many cells self-renew to maintain the pool, and which proliferate and become committed to give rise to the mature blood elements, are still unclear.

Multipotent Stem Cells in the Adult Central Nervous System

Questions have been raised regarding the existence and location of true stem cells in the CNS, which may be able to sustain adult neurogenesis continuously and may even provide an endogenous source of new neural Cells in the course of reparative processes.

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Because they have the dual ability to proliferate indefinitely and differentiate into multiple tissue types, human ES cells could potentially provide an unlimited supply of tissue for human transplantation.



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While the majority of Thy-1loLin-Sca-1+ bone marrow cells whose progeny are detected in the in vivo repopulation assay are pluripotential, only a subset undergo long-term self-renewal in vivo, bringing into question the notion that steady-state hematopoiesis in normal individuals is oligoclonal.

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The findings indicate that a gene mapping to this region is mutated in either C57BL/6 or DBA/2 (and possibly AKR) mice, which may facilitate the identification of a gene implicated in human 5q-syndromes.

The Role of Apoptosis in the Regulation of Hematopoietic Stem Cells

A transgenic mouse model that overexpresses BCL-2 in all hematopoietic cells, including HSC, is employed, showing that cells from H2K-BCL-2 mice have an increased plating efficiency in vitro, engraft at least as well as wild-type HSC in vivo, and have an advantage following competitive reconstitution with wild- type HSC.

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This study shows that the same populations, with similar functional activities, exist in mice whose hematopoietic systems were reconstituted by hematopolietic stem cells after lethal irradiation, and demonstrates that these populations form a lineage of multipotent progenitors from long-term self-renewing stem cells to the most mature multip powerless progenitor population.

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By extrapolation, the rare human Thy-1+Lin-CD34+ cell population contains pluripotent hematopoietic progenitors; it is proposed that it is highly enriched for candidate hematopolietic stem cells.