Clonal and Quantitative In Vivo Assessment of Hematopoietic Stem Cell Differentiation Reveals Strong Erythroid Potential of Multipotent Cells
Clonal and Quantitative In Vivo Assessment of Hematopoietic Stem Cell Differentiation Reveals Strong Erythroid Potential of Multipotent Cells
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DOI：
10.1016/j.stemcr.2019.02.007
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发表时间：
2019-04-09
影响因子：
5.9
通讯作者：
Forsberg, E. Camilla
中科院分区：
文献类型：
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作者：
Boyer, Scott W.;Rajendiran, Smrithi;Forsberg, E. Camilla
造血可以说是最被理解的干细胞系统之一；然而，在对造血干细胞和造血祖细胞群体的谱系潜力、异质性和关系达成共识方面仍然存在重大挑战。为了获得新的见解，我们对造血干细胞(HSCs)和多个造血祖细胞群体的成熟细胞生产进行了定量分析。对每个祖细胞产生的成熟细胞类型的绝对数量的评估显示，所有被评估的具有髓系能力的祖细胞都具有显著的红系优势，并伴有强烈的血小板重建。所有具有髓系潜能的人群在体内也产生了大量的红细胞和血小板。通过单细胞移植和脾集落分析的克隆分析表明，很大一部分HSCs和多能祖细胞在单细胞水平上具有多系潜能。这些新的见解促进了一种以红系为重点的造血分化模型。
Hematopoiesis is arguably one of the best understood stem cell systems; however, significant challenges remain to reach a consensus understanding of the lineage potential, heterogeneity, and relationships of hematopoietic stem and progenitor cell populations. To gain new insights, we performed quantitative analyses of mature cell production from hematopoietic stem cells (HSCs) and multiple hematopoietic progenitor populations. Assessment of the absolute numbers of mature cell types produced by each progenitor cell revealed a striking erythroid dominance of all myeloid-competent progenitors assessed, accompanied by strong platelet reconstitution. All populations with myeloid potential also produced robust numbers of red blood cells and platelets in vivo. Clonal analysis by single-cell transplantation and by spleen colony assays revealed that a significant fraction of HSCs and multipotent progenitors have multilineage potential at the single-cell level. These new insights prompt an erythroid-focused model of hematopoietic differentiation.