3032 – MOUSE MULTIPOTENT PROGENITOR 5 CELLS ARE LOCATED AT THE INTERPHASE BETWEEN HEMATOPOIETIC STEM AND PROGENITOR CELLS

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+ C...

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Veröffentlicht in:Experimental hematology Jg. 100; S. S58
Hauptverfasser: Sommerkamp, Pia, Romero-Mulero, Mari Carmen, Narr, Andreas, Ladel, Luisa, Hustin, Lucie, Schönberger, Katharina, Renders, Simon, Altamura, Sandro, Zeisberger, Petra, Jäcklein, Karin, Klimmeck, Daniel, Rodriguez-Fraticelli, Alejo, Camargo, Fernando, Perié, Leïla, Trumpp, Andreas, Cabezas-Wallscheid, Nina
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Elsevier Inc 01.08.2021
Schlagworte:
Advanced Basic Science
Hematology, Oncology, and Palliative Medicine
ISSN:0301-472X, 1873-2399
Online-Zugang:Volltext
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Zusammenfassung: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-) and MPP6 (LSK CD34- CD135- CD48- CD150-) (Sommerkamp et al., Blood 2021). Upon transplantation, MPP5 supports initial emergency myelopoiesis followed by stable contribution to the lymphoid lineage, while MPP6 exhibits a more stem cell-like behavior. 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 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.
ISSN:0301-472X
1873-2399
DOI:10.1016/j.exphem.2021.12.253