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Updated: Sep 8, 2025

Directed Differentiation of Primitive and Definitive Hematopoietic Progenitors from Human Pluripotent Stem Cells
Published on: November 1, 2017
A single-cell framework identifies functionally and molecularly distinct multipotent progenitors in adult human
Asiri Ediriwickrema1, Yusuke Nakauchi2, Amy C Fan3
1Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA; Cancer Biology Graduate Program, Stanford University, Stanford, CA, USA; Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
None:
Hematopoietic multipotent progenitors (MPPs) regulate blood cell production to meet the evolving demands of an organism. Adult human MPPs remain ill defined, whereas mouse MPPs are well characterized, with distinct immunophenotypes and lineage potencies. Using multi-omic single-cell analyses and functional assays, we identified distinct human MPPs within Lin-CD34+CD38dim/lo adult bone marrow with unique biomolecular and functional properties. These populations were prospectively isolated based on expression of CD69, CLL1, and CD2 in addition to classical markers like CD90 and CD45RA. We identified a CD69+ MPP with long-term engraftment and multilineage differentiation potential, a CLL1+ myeloid-biased MPP, and a CLL1-CD69- erythroid-biased MPP. We used this updated hematopoietic stem and progenitor cell (HSPC) profile to study human and mouse bone marrow cells and observe unique cell-type-specific homology between species and cell-type-specific changes associated with human aging. By identifying and functionally characterizing adult MPP sub-populations, we provide a framework for future studies in hematopoiesis.
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