Mouse Multipotent Progenitor 5 Cells Are Located at the Interphase Between Hematopoietic Stem and Progenitor Cells

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2021 Mar 23

PMID 33754628

Citations 25

Authors

Pia Sommerkamp

Mari Carmen Romero-Mulero

Andreas Narr

Luisa Ladel

Lucie Hustin

Katharina Schonberger

Simon Renders

Sandro Altamura

Petra Zeisberger

Karin Jacklein

Daniel Klimmeck

Alejo Rodriguez-Fraticelli

Fernando D Camargo

Leila Perie

Andreas Trumpp

Nina Cabezas-Wallscheid

Affiliations

Soon will be listed here.

Abstract

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.

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