TY - JOUR
T1 - A single-cell framework identifies functionally and molecularly distinct multipotent progenitors in adult human hematopoiesis
AU - A.S. Ediriwickrema, Asiri Saumya
AU - Y. Nakauchi, Yusuke
AU - A.C. Fan, Amy C.
AU - T. Köhnke, Thomas
AU - X. Hu, Xiaoyi
AU - B.A. Luca, Bogdan Alexandru
AU - Y. Kim, Ye-eun
AU - S. Ramakrishnan, Sreejith
AU - M.A. Nakamoto, Margaret A.
AU - D. Karigane, Daiki
PY - 2025
Y1 - 2025
N2 - 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. © 2025 Elsevier B.V., All rights reserved.
AB - 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. © 2025 Elsevier B.V., All rights reserved.
U2 - 10.1016/j.celrep.2025.116236
DO - 10.1016/j.celrep.2025.116236
M3 - Article
SN - 2211-1247
VL - 44
JO - Cell Reports
JF - Cell Reports
IS - 9
ER -