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  • Rodewald, Hans-Reimer  (3)
  • Medicine  (3)
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  • Medicine  (3)
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  • 1
    Online Resource
    Online Resource
    Annual Reviews ; 2016
    In:  Annual Review of Immunology Vol. 34, No. 1 ( 2016-05-20), p. 449-478
    In: Annual Review of Immunology, Annual Reviews, Vol. 34, No. 1 ( 2016-05-20), p. 449-478
    Abstract: Hematopoietic stem cells (HSCs) and downstream progenitors have long been studied based on phenotype, cell purification, proliferation, and transplantation into myeloablated recipients. These experiments, complemented by data on expression profiles, mouse mutants, and humans with hematopoietic defects, are the foundation for the current hematopoietic differentiation tree. However, there are fundamental gaps in our knowledge of the quantitative and qualitative operation of the HSC/progenitor system under physiological and pathological conditions in vivo. The hallmarks of HSCs, self-renewal and multipotency, are observed in in vitro assays and cell transplantation experiments; however, the extent to which these features occur naturally in HSCs and progenitors remains uncertain. We focus here on work that strives to address these unresolved questions, with emphasis on fate mapping and modeling of the hematopoietic flow from stem cells toward myeloid and lymphoid lineages during development and adult life.
    Type of Medium: Online Resource
    ISSN: 0732-0582 , 1545-3278
    URL: Issue
    RVK:
    Language: English
    Publisher: Annual Reviews
    Publication Date: 2016
    detail.hit.zdb_id: 1470451-1
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    American Society of Hematology ; 2018
    In:  Blood Vol. 132, No. 11 ( 2018-09-13), p. 1106-1113
    In: Blood, American Society of Hematology, Vol. 132, No. 11 ( 2018-09-13), p. 1106-1113
    Abstract: Advances in genetic labeling and barcoding of hematopoietic stem cells (HSCs) in situ now allow direct measurements of physiological HSC output, both quantitatively and qualitatively. Turning on a heritable label in HSCs and measuring the kinetics of label emergence in downstream compartments reveal rates of differentiation and self-renewal of HSCs and progenitor cells, whereas endogenous HSC barcoding probes physiological precursor-product relationships. Labels have been inserted at different stages of the hematopoietic differentiation hierarchy. Recent genetic and functional evidence suggests a phenotype (Tie2+) for tip HSCs. Fate mapping shows that many tip HSCs regularly feed into downstream stages, with individual cells contributing infrequently. Stem and progenitor cells downstream of tip HSCs serve as a major, nearly self-renewing source of day-to-day hematopoiesis, rendering the blood and immune system HSC-independent for extended periods of time. HSCs realize multilineage output, yet, fates restricted to several lineages or even a single lineage have also been observed. Single HSCs within a clone in the bone marrow that develop from a fetal HSC precursor have been observed to express clone-specific fates. Thus, the new tools probing HSC differentiation in situ are progressing beyond assays for HSC activity based on proliferation measurements and fates of transplanted stem cells, and the data challenge lineage interpretations of single-cell gene expression snapshots. Linking in vivo fate analyses to gene expression and other molecular determinants of cell fate will aid in unraveling the mechanisms of lineage commitment and the architecture of physiological hematopoiesis.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    Online Resource
    Online Resource
    Elsevier BV ; 2017
    In:  Experimental Hematology Vol. 53 ( 2017-09), p. S26-
    In: Experimental Hematology, Elsevier BV, Vol. 53 ( 2017-09), p. S26-
    Type of Medium: Online Resource
    ISSN: 0301-472X
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 2005403-8
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