A single-cell framework identifies functionally and molecularly distinct multipotent progenitors in adult human hematopoiesis

作者：Asiri Ediriwickrema, Yusuke Nakauchi, Amy C. Fan, Thomas Köhnke, Xiaoyi Hu, Bogdan Luca, YeEun Kim, Sreejith Ramakrishnan, Margaret Nakamoto, Daiki Karigane, Miles H. Linde, Armon Azizi, Aaron M. Newman, Andrew J. Gentles, Ravindra Majeti · 发表于：Cell Reports · 年份：2025 · DOI：10.1016/j.celrep.2025.116236 · 被引用次数：4 · 研究领域：Single-cell and spatial transcriptomics、Hematopoietic Stem Cell Transplantation、Acute Myeloid Leukemia Research

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.