Fundamental properties of unperturbed haematopoiesis from stem cells in vivo.
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| Title: | Fundamental properties of unperturbed haematopoiesis from stem cells in vivo. |
|---|---|
| Authors: | Busch, Katrin, Klapproth, Kay, Barile, Melania, Flossdorf, Michael, Holland-Letz, Tim, Schlenner, Susan M., Reth, Michael, Höfer, Thomas, Rodewald, Hans-Reimer |
| Source: | Nature. 2/25/2015, Vol. 518 Issue 7540, p542-546. 5p. 1 Chart, 14 Graphs. |
| Subjects: | Hematopoietic stem cells, Stem cell transplantation research, Human chromosomes, Immune system, Hematopoiesis |
| Abstract: | Haematopoietic stem cells (HSCs) are widely studied by HSC transplantation into immune- and blood-cell-depleted recipients. Single HSCs can rebuild the system after transplantation. Chromosomal marking, viral integration and barcoding of transplanted HSCs suggest that very low numbers of HSCs perpetuate a continuous stream of differentiating cells. However, the numbers of productive HSCs during normal haematopoiesis, and the flux of differentiating progeny remain unknown. Here we devise a mouse model allowing inducible genetic labelling of the most primitive Tie2+ HSCs in bone marrow, and quantify label progression along haematopoietic development by limiting dilution analysis and data-driven modelling. During maintenance of the haematopoietic system, at least 30% or ∼5,000 HSCs are productive in the adult mouse after label induction. However, the time to approach equilibrium between labelled HSCs and their progeny is surprisingly long, a time scale that would exceed the mouse's life. Indeed, we find that adult haematopoiesis is largely sustained by previously designated 'short-term' stem cells downstream of HSCs that nearly fully self-renew, and receive rare but polyclonal HSC input. By contrast, in fetal and early postnatal life, HSCs are rapidly used to establish the immune and blood system. In the adult mouse, 5-fluoruracil-induced leukopenia enhances the output of HSCs and of downstream compartments, thus accelerating haematopoietic flux. Label tracing also identifies a strong lineage bias in adult mice, with several-hundred-fold larger myeloid than lymphoid output, which is only marginally accentuated with age. Finally, we show that transplantation imposes severe constraints on HSC engraftment, consistent with the previously observed oligoclonal HSC activity under these conditions. Thus, we uncover fundamental differences between the normal maintenance of the haematopoietic system, its regulation by challenge, and its re-establishment after transplantation. HSC fate mapping and its linked modelling provide a quantitative framework for studying in situ the regulation of haematopoiesis in health and disease. [ABSTRACT FROM AUTHOR] |
| Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 101169467 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Fundamental properties of unperturbed haematopoiesis from stem cells in vivo. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Busch%2C+Katrin%22">Busch, Katrin</searchLink><br /><searchLink fieldCode="AR" term="%22Klapproth%2C+Kay%22">Klapproth, Kay</searchLink><br /><searchLink fieldCode="AR" term="%22Barile%2C+Melania%22">Barile, Melania</searchLink><br /><searchLink fieldCode="AR" term="%22Flossdorf%2C+Michael%22">Flossdorf, Michael</searchLink><br /><searchLink fieldCode="AR" term="%22Holland-Letz%2C+Tim%22">Holland-Letz, Tim</searchLink><br /><searchLink fieldCode="AR" term="%22Schlenner%2C+Susan+M%2E%22">Schlenner, Susan M.</searchLink><br /><searchLink fieldCode="AR" term="%22Reth%2C+Michael%22">Reth, Michael</searchLink><br /><searchLink fieldCode="AR" term="%22Höfer%2C+Thomas%22">Höfer, Thomas</searchLink><br /><searchLink fieldCode="AR" term="%22Rodewald%2C+Hans-Reimer%22">Rodewald, Hans-Reimer</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Nature%22">Nature</searchLink>. 2/25/2015, Vol. 518 Issue 7540, p542-546. 5p. 1 Chart, 14 Graphs. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Hematopoietic+stem+cells%22">Hematopoietic stem cells</searchLink><br /><searchLink fieldCode="DE" term="%22Stem+cell+transplantation+research%22">Stem cell transplantation research</searchLink><br /><searchLink fieldCode="DE" term="%22Human+chromosomes%22">Human chromosomes</searchLink><br /><searchLink fieldCode="DE" term="%22Immune+system%22">Immune system</searchLink><br /><searchLink fieldCode="DE" term="%22Hematopoiesis%22">Hematopoiesis</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Haematopoietic stem cells (HSCs) are widely studied by HSC transplantation into immune- and blood-cell-depleted recipients. Single HSCs can rebuild the system after transplantation. Chromosomal marking, viral integration and barcoding of transplanted HSCs suggest that very low numbers of HSCs perpetuate a continuous stream of differentiating cells. However, the numbers of productive HSCs during normal haematopoiesis, and the flux of differentiating progeny remain unknown. Here we devise a mouse model allowing inducible genetic labelling of the most primitive Tie2+ HSCs in bone marrow, and quantify label progression along haematopoietic development by limiting dilution analysis and data-driven modelling. During maintenance of the haematopoietic system, at least 30% or ∼5,000 HSCs are productive in the adult mouse after label induction. However, the time to approach equilibrium between labelled HSCs and their progeny is surprisingly long, a time scale that would exceed the mouse's life. Indeed, we find that adult haematopoiesis is largely sustained by previously designated 'short-term' stem cells downstream of HSCs that nearly fully self-renew, and receive rare but polyclonal HSC input. By contrast, in fetal and early postnatal life, HSCs are rapidly used to establish the immune and blood system. In the adult mouse, 5-fluoruracil-induced leukopenia enhances the output of HSCs and of downstream compartments, thus accelerating haematopoietic flux. Label tracing also identifies a strong lineage bias in adult mice, with several-hundred-fold larger myeloid than lymphoid output, which is only marginally accentuated with age. Finally, we show that transplantation imposes severe constraints on HSC engraftment, consistent with the previously observed oligoclonal HSC activity under these conditions. Thus, we uncover fundamental differences between the normal maintenance of the haematopoietic system, its regulation by challenge, and its re-establishment after transplantation. HSC fate mapping and its linked modelling provide a quantitative framework for studying in situ the regulation of haematopoiesis in health and disease. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1038/nature14242 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 5 StartPage: 542 Subjects: – SubjectFull: Hematopoietic stem cells Type: general – SubjectFull: Stem cell transplantation research Type: general – SubjectFull: Human chromosomes Type: general – SubjectFull: Immune system Type: general – SubjectFull: Hematopoiesis Type: general Titles: – TitleFull: Fundamental properties of unperturbed haematopoiesis from stem cells in vivo. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Busch, Katrin – PersonEntity: Name: NameFull: Klapproth, Kay – PersonEntity: Name: NameFull: Barile, Melania – PersonEntity: Name: NameFull: Flossdorf, Michael – PersonEntity: Name: NameFull: Holland-Letz, Tim – PersonEntity: Name: NameFull: Schlenner, Susan M. – PersonEntity: Name: NameFull: Reth, Michael – PersonEntity: Name: NameFull: Höfer, Thomas – PersonEntity: Name: NameFull: Rodewald, Hans-Reimer IsPartOfRelationships: – BibEntity: Dates: – D: 25 M: 02 Text: 2/25/2015 Type: published Y: 2015 Identifiers: – Type: issn-print Value: 00280836 Numbering: – Type: volume Value: 518 – Type: issue Value: 7540 Titles: – TitleFull: Nature Type: main |
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