Distinct routes of lineage development reshape the human blood hierarchy across ontogeny

single cell sequencing;SNS;单细胞测序;单细胞多组学
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Faiyaz Notta #, Sasan Zandi #, Naoya Takayama, Stephanie Dobson, Olga I Gan, Gavin Wilson, Kerstin B Kaufmann, Jessica McLeod, Elisa Laurenti, Cyrille F Dunant, John D McPherson, Lincoln D Stein, Yigal Dror, John E Dick

  • Science
  • 2016
  • 63.714
  • 351(6269):aab2116.
  • Human
  • 单细胞测序
  • Myeloid cell
  • 技术分享
  • 其它细胞
  • ITA2B, GP1BA
  • UBERON_0000178

Abstract

In a classical view of hematopoiesis, the various blood cell lineages arise via a hierarchical scheme starting with multipotent stem cells that become increasingly restricted in their differentiation potential through oligopotent and then unipotent progenitors. We developed a cell-sorting scheme to resolve myeloid (My), erythroid (Er), and megakaryocytic (Mk) fates from single CD34(+) cells and then mapped the progenitor hierarchy across human development. Fetal liver contained large numbers of distinct oligopotent progenitors with intermingled My, Er, and Mk fates. However, few oligopotent progenitor intermediates were present in the adult bone marrow. Instead, only two progenitor classes predominate, multipotent and unipotent, with Er-Mk lineages emerging from multipotent cells. The developmental shift to an adult "two-tier" hierarchy challenges current dogma and provides a revised framework to understand normal and disease states of human hematopoiesis.
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