Clonal analysis of lineage fate in native haematopoiesis
Rodriguez-Fraticelli, Alejo E.1,2; Wolock, Samuel L.3; Weinreb, Caleb S.3; Panero, Riccardo4; Patel, Sachin H.1; Jankovic, Maja1; Sun, Jianlong1,2,5; Calogero, Raffaele A.4; Klein, Allon M.3; Camargo, Fernando D.1,2
2018-01-11
发表期刊NATURE
ISSN0028-0836
卷号553期号:7687页码:212-+
发表状态已发表
DOI10.1038/nature25168
摘要Haematopoiesis, the process of mature blood and immune cell production, is functionally organized as a hierarchy, with self-renewing haematopoietic stem cells and multipotent progenitor cells sitting at the very top(1,2). Multiple models have been proposed as to what the earliest lineage choices are in these primitive haematopoietic compartments, the cellular intermediates, and the resulting lineage trees that emerge from them(3-10). Given that the bulk of studies addressing lineage outcomes have been performed in the context of haematopoietic transplantation, current models of lineage branching are more likely to represent roadmaps of lineage potential than native fate. Here we use transposon tagging to clonally trace the fates of progenitors and stem cells in unperturbed haematopoiesis. Our results describe a distinct clonal roadmap in which the megakaryocyte lineage arises largely independently of other haematopoietic fates. Our data, combined with single-cell RNA sequencing, identify a functional hierarchy of unilineage- and oligolineage-producing clones within the multipotent progenitor population. Finally, our results demonstrate that traditionally defined long-term haematopoietic stem cells are a significant source of megakaryocyte-restricted progenitors, suggesting that the megakaryocyte lineage is the predominant native fate of long-term haematopoietic stem cells. Our study provides evidence for a substantially revised roadmap for unperturbed haematopoiesis, and highlights unique properties of multipotent progenitors and haematopoietic stem cells in situ.
收录类别SCI ; SCIE
语种英语
资助项目National Institutes of Health[HL128850-01A1] ; National Institutes of Health[P01HL13147]
WOS研究方向Science & Technology - Other Topics
WOS类目Multidisciplinary Sciences
WOS记录号WOS:000419794800038
出版者NATURE PUBLISHING GROUP
WOS关键词SINGLE-CELL TRANSCRIPTOMICS ; STEM-CELLS ; MULTIPOTENT PROGENITORS ; IDENTIFICATION ; COMMITMENT ; MEGAKARYOCYTES ; CLASSIFICATION ; SUBPOPULATIONS ; HETEROGENEITY ; HIERARCHY
原始文献类型Article
引用统计
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/16253
专题生命科学与技术学院_PI研究组_孙建龙组
通讯作者Camargo, Fernando D.
作者单位1.Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA
2.Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
3.Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA
4.Univ Torino, Dept Clin & Biol Sci, Ctr Mol Biotechnol, I-10126 Turin, Italy
5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
推荐引用方式
GB/T 7714
Rodriguez-Fraticelli, Alejo E.,Wolock, Samuel L.,Weinreb, Caleb S.,et al. Clonal analysis of lineage fate in native haematopoiesis[J]. NATURE,2018,553(7687):212-+.
APA Rodriguez-Fraticelli, Alejo E..,Wolock, Samuel L..,Weinreb, Caleb S..,Panero, Riccardo.,Patel, Sachin H..,...&Camargo, Fernando D..(2018).Clonal analysis of lineage fate in native haematopoiesis.NATURE,553(7687),212-+.
MLA Rodriguez-Fraticelli, Alejo E.,et al."Clonal analysis of lineage fate in native haematopoiesis".NATURE 553.7687(2018):212-+.
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