Title: A single cell framework identifies functionally and molecularly distinct multipotent progenitors in adult human hematopoiesis Authors: Asiri Ediriwickrema, Yusuke Nakauchi, Amy C. Fan, Thomas Köhnke, Xiaoyi Hu, Bogdan A. Luca, YeEun Kim, Sreejith Ramakrishnan, Margaret Nakamoto, Daiki Karigane, Miles H. Linde, Armon Azizi, Aaron M. Newman, Andrew J. Gentles, Ravindra Majeti
Cell Rep. 2025 Sep 23;44(9):116236. doi: 10.1016/j.celrep.2025.116236. Epub 2025 Sep 3. PMID: 40911415. DOI: 10.1016/j.celrep.2025.116236
Hematopoietic multipotent progenitors (MPPs) regulate blood cell production to appropriately meet the biological demands of the human body. Human MPPs remain ill-defined whereas mouse MPPs have been well characterized with distinct immunophenotypes and lineage potencies. Using multiomic single cell analyses and complementary functional assays, we identified new human MPPs and oligopotent progenitor populations within Lin-CD34+CD38dim/lo adult bone marrow with distinct 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 show that within the canonical Lin-CD34+CD38dim/loCD90-CD45RA- MPP population, there is a CD69+ MPP with long-term engraftment and multilineage differentiation potential, a CLL1+ myeloid-biased MPP, and a CLL1-CD69- erythroid-biased MPP. We also show that the canonical Lin-CD34+CD38dim/loCD90-CD45RA+ LMPP population can be separated into a CD2+ LMPP with lymphoid and myeloid potential, a CD2- LMPP with high lymphoid potential, and a CLL1+ GMP with minimal lymphoid potential. We used these new HSPC profiles to study human and mouse bone marrow cells and observe unique cell type specific homology between humans and mice and cell type specific changes associated with aging. By identifying and functionally characterizing adult MPP sub-populations, we provide a new framework for future studies in human hematopoiesis.
Reference scripts for the analyses described in the mansucript can be found in the markdown_scripts folder.
The meta data for the reference is provided in the RDS object below, and the meta data for the ARCHR project is located in the meta directory.
The raw data for the newly generated single cell data will be deposited in dbGaP under accession phs003690.v1.p1 and the processed UMI tables are available under GEO accession GSE262440.
Link to reference single cell dataset:
The RNA assay contains the original WTA and ADT counts. The ADT assay contains the original ADT counts. The soupx_counts assay contains SoupX corrected WTA and ADT counts while the soupx_wta_only assay contains SoupX corrected RNA counts.
Please contact the authors (asiri.e@gmail.com) with questions and or requests for additional data.