Abstract：
:Haematopoietic stem cells (HSCs) arise in the developing aorta during embryogenesis. The number of HSC clones born has been estimated through transplantation, but experimental approaches to assess the absolute number of forming HSCs in a native setting have remained challenging. Here, we applied single-cell and clonal analysis of HSCs in zebrafish to quantify developing HSCs. Targeting creERT2 in developing cd41:eGFP+ HSCs enabled long-term assessment of their blood contribution. We also applied the Brainbow-based multicolour Zebrabow system with drl:creERT2 that is active in early haematopoiesis to induce heritable colour barcoding unique to each HSC and its progeny. Our findings reveal that approximately 21 HSC clones exist prior to HSC emergence and 30 clones are present during peak production from aortic endothelium. Our methods further reveal that stress haematopoiesis, including sublethal irradiation and transplantation, reduces clonal diversity. Our findings provide quantitative insights into the early clonal events that regulate haematopoietic development.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Henninger J,Santoso B,Hans S,Durand E,Moore J,Mosimann C,Brand M,Traver D,Zon Ldoi
10.1038/ncb3444subject
Has Abstractpub_date
2017-01-01 00:00:00pages
17-27issue
1eissn
1465-7392issn
1476-4679pii
ncb3444journal_volume
19pub_type
杂志文章abstract：:Unrepaired DNA double-strand breaks (DSBs) cause genetic instability that leads to malignant transformation or cell death. Cells respond to DSBs with the ordered recruitment of signalling and repair proteins to the site of lesion. Protein modification with ubiquitin is crucial for the signalling cascade, but how ubiqu...
journal_title：Nature cell biology
pub_type： 杂志文章
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abstract：:Nutrient availability is central for T-cell functions and immune responses. Here we report that CD8+ T-cell activation and anti-tumour responses are strongly potentiated by the non-essential amino acid Asn. Increased Asn levels enhance CD8+ T-cell activation and effector functions against tumour cells in vitro and in ...
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journal_title：Nature cell biology
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pub_type： 杂志文章,评审
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更新日期：2018-07-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2002-09-01 00:00:00
abstract：:The spindle checkpoint ensures accurate chromosome segregation by delaying cell-cycle progression until all sister kinetochores capture microtubules from opposite poles and come under tension (for reviews, see refs 1, 2). Although the checkpoint is activated by either the lack of kinetochore-microtubule attachments or...
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更新日期：2017-05-31 00:00:00
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pub_type： 杂志文章
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journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/ncb2548
更新日期：2012-08-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1433
更新日期：2006-07-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3111
更新日期：2015-04-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2126
更新日期：2010-12-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3390
更新日期：2016-08-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1061
更新日期：2003-11-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2719
更新日期：2013-05-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1774
更新日期：2008-10-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1899
更新日期：2009-07-01 00:00:00
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journal_title：Nature cell biology
pub_type： 评论,杂志文章
doi：10.1038/ncb1008-1131
更新日期：2008-10-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2204
更新日期：2011-04-01 00:00:00
abstract：:Pluripotent stem cells (PSCs) may provide a potential source of haematopoietic stem/progenitor cells (HSPCs) for transplantation; however, unknown molecular barriers prevent the self-renewal of PSC-HSPCs. Using two-step differentiation, human embryonic stem cells (hESCs) differentiated in vitro into multipotent haemat...
journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2016-06-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2014-01-01 00:00:00
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pub_type： 评论,杂志文章
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更新日期：2014-11-01 00:00:00
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更新日期：2009-08-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2004-06-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2009-10-01 00:00:00
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journal_title：Nature cell biology
pub_type： 评论,杂志文章
doi：10.1038/ncb3086
更新日期：2015-01-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2015-07-01 00:00:00
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journal_title：Nature cell biology
pub_type： 新闻
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更新日期：2012-10-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2015-02-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2018-10-01 00:00:00
