Characterization and generation of human definitive multipotent hematopoietic stem/progenitor cells
Open Access
- 1 December 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Discovery
- Vol. 6 (1), 1-18
- https://doi.org/10.1038/s41421-020-00213-6
Abstract
Definitive hematopoiesis generates hematopoietic stem/progenitor cells (HSPCs) that give rise to all mature blood and immune cells, but remains poorly defined in human. Here, we resolve human hematopoietic populations at the earliest hematopoiesis stage by single-cell RNA-seq. We characterize the distinct molecular profiling between early primitive and definitive hematopoiesis in both human embryonic stem cell (hESC) differentiation and early embryonic development. We identify CD44 to specifically discriminate definitive hematopoiesis and generate definitive HSPCs from hESCs. The multipotency of hESCs-derived HSPCs for various blood and immune cells is validated by single-cell clonal assay. Strikingly, these hESCs-derived HSPCs give rise to blood and lymphoid lineages in vivo. Lastly, we characterize gene-expression dynamics in definitive and primitive hematopoiesis and reveal an unreported role of ROCK-inhibition in enhancing human definitive hematopoiesis. Our study provides a prospect for understanding human early hematopoiesis and a firm basis for generating blood and immune cells for clinical purposes.This publication has 38 references indexed in Scilit:
- Decoding human fetal liver haematopoiesisNature, 2019
- Early Human Hemogenic Endothelium Generates Primitive and Definitive Hematopoiesis In VitroStem Cell Reports, 2018
- Causes and Consequences of Hematopoietic Stem Cell HeterogeneityCell Stem Cell, 2018
- Single-cell analysis reveals the continuum of human lympho-myeloid progenitor cellsNature Immunology, 2017
- Distinct routes of lineage development reshape the human blood hierarchy across ontogenyScience, 2016
- Human definitive haemogenic endothelium and arterial vascular endothelium represent distinct lineagesNature, 2015
- The transcriptional architecture of early human hematopoiesis identifies multilevel control of lymphoid commitmentNature Immunology, 2013
- In vivo imaging of haematopoietic cells emerging from the mouse aortic endotheliumNature, 2010
- Identification of a Hierarchy of Multipotent Hematopoietic Progenitors in Human Cord BloodCell Stem Cell, 2007
- Graded Levels of GATA-1 Expression Modulate Survival, Proliferation, and Differentiation of Erythroid ProgenitorsOnline Journal of Public Health Informatics, 2005