Mouse multipotent progenitor 5 cells are located at the interphase between hematopoietic stem and progenitor cells

Nom de la revue
Pia Sommerkamp, Mari Carmen Romero-Mulero, Andreas Narr, Luisa Ladel, Lucie Hustin, Katharina Schönberger, Simon Renders, Sandro Altamura, Petra Zeisberger, Karin Jäcklein, Daniel Klimmeck, Alejo Rodriguez-Fraticelli, Fernando D. Camargo, Leïla Perié, Andreas Trumpp, Nina Cabezas-Wallscheid

Hematopoietic stem cells (HSCs) and distinct multipotent progenitor (MPP) populations (MPP1-4) contained within the Lin−Sca-1+c-Kit+ (LSK) compartment have previously been identified using diverse surface-marker panels. Here, we phenotypically define and functionally characterize MPP5 (LSK CD34+CD135−CD48−CD150−). Upon transplantation, MPP5 supports initial emergency myelopoiesis followed by stable contribution to the lymphoid lineage. MPP5, capable of generating MPP1-4 but not HSCs, represents a dynamic and versatile component of the MPP network. To characterize all hematopoietic stem and progenitor cells, we performed RNA-sequencing (RNA-seq) analysis to identify specific transcriptomic landscapes of HSCs and MPP1-5. This was complemented by single-cell RNA-seq analysis of LSK cells to establish the differentiation trajectories from HSCs to MPP1-5. In agreement with functional reconstitution activity, MPP5 is located immediately downstream of HSCs but upstream of the more committed MPP2-4. This study provides a comprehensive analysis of the LSK compartment, focusing on the functional and molecular characteristics of the newly defined MPP5 subset.