3171 – MOUSE MULTIPOTENT PROGENITOR 5 CELLS ARE LOCATED AT THE INTERPHASE BETWEEN HEMATOPOIETIC STEM AND PROGENITOR CELLS

• Published in: Experimental hematology Vol. 111; p. S130
• Main Authors: Romero-Mulero, Mari Carmen, Sommerkamp, Pia, Narr, Andreas, Ladel, Luisa, Hustin, Lucie, Schoenberger, Katharina, Renders, Simon, Altamura, Sandro, Zeisberger, Petra, Jaecklein, Karin, Klimmeck, Daniel, Rodriguez-Fraticelli, Alejo, Camargo, Fernando D., Perie, Leïla, Trumpp, Andreas, Cabezas-Wallscheid, Nina
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 2022
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2022.07.227

Hematopoietic stem cells (HSCs) are located at the top of the hematopoietic hierarchy and, together with multipotent progenitors (MPPs), are contained within the Lin−Sca-1+c-Kit+ (LSK) compartment. We and others have previously characterized HSCs and MPP1-4 using diverse surface-marker panels. In this study we address the molecular (RNA-seq at population and single-cell level) and functional (in vivo and in vitro) characterization of the previously unknown MPP5 population (LSK CD34+ CD135- CD48- CD150-; Sommerkamp*, Romero-Mulero* et al., Blood 2021; *first-shared authorship). Upon transplantation, MPP5 cells presented in vivo a distinctive engraftment pattern supporting initial emergency myelopoiesis but long-term contribution to the lymphoid lineage. In addition, in vitro assays showed that MPP5 cells are immediately downstream of the stem cell compartment and represent a dynamic component of the MPP network, as they are capable of generating MPP1-4 populations, but not HSCs. To identify specific transcriptomic landscapes of hematopoietic stem and progenitor cells (HSPCs), we performed RNA-sequencing (RNA-seq) analysis of HSCs and MPP1-5. Expression patterns of MPP5 were similar to HSC and MPP1 populations and were primed towards inflammatory processes. This was complemented by extensive single-cell RNA-seq (scRNA-seq) analysis of the LSK compartment to establish the differentiation trajectories from HSCs to MPP1-5. In agreement with functional assays, MPP5 population is located immediately downstream of HSCs but upstream of the more committed MPP2-4, displaying trajectories to all the different MPP populations. This study provides a comprehensive analysis of the whole classically gated LSK compartment, focusing on the functional and molecular characteristics of the MPP5 subset.