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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| Published in: | Experimental hematology Vol. 100; p. S58 |
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| Main Authors: | , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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Elsevier Inc
01.08.2021
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| ISSN: | 0301-472X, 1873-2399 |
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| 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-) 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. |
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| AbstractList | 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. |
| Author | Ladel, Luisa Rodriguez-Fraticelli, Alejo Klimmeck, Daniel Narr, Andreas Sommerkamp, Pia Camargo, Fernando Cabezas-Wallscheid, Nina Jäcklein, Karin Zeisberger, Petra Trumpp, Andreas Renders, Simon Altamura, Sandro Schönberger, Katharina Perié, Leïla Romero-Mulero, Mari Carmen Hustin, Lucie |
| Author_xml | – sequence: 1 givenname: Pia surname: Sommerkamp fullname: Sommerkamp, Pia organization: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany, Heidelberg, Germany – sequence: 2 givenname: Mari Carmen surname: Romero-Mulero fullname: Romero-Mulero, Mari Carmen organization: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany, Germany – sequence: 3 givenname: Andreas surname: Narr fullname: Narr, Andreas organization: Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Germany – sequence: 4 givenname: Luisa surname: Ladel fullname: Ladel, Luisa organization: Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany, Germany – sequence: 5 givenname: Lucie surname: Hustin fullname: Hustin, Lucie organization: Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie, 75005 Paris, France, France – sequence: 6 givenname: Katharina surname: Schönberger fullname: Schönberger, Katharina organization: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany, Germany – sequence: 7 givenname: Simon surname: Renders fullname: Renders, Simon organization: Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Germany – sequence: 8 givenname: Sandro surname: Altamura fullname: Altamura, Sandro organization: Department of Pediatric Hematology, Oncology and Immunology, Heidelberg University Medical Center, 69120 Heidelberg, Germany, Germany – sequence: 9 givenname: Petra surname: Zeisberger fullname: Zeisberger, Petra organization: Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) andHeidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany, Germany – sequence: 10 givenname: Karin surname: Jäcklein fullname: Jäcklein, Karin organization: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany, Germany – sequence: 11 givenname: Daniel surname: Klimmeck fullname: Klimmeck, Daniel organization: Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany, Germany – sequence: 12 givenname: Alejo surname: Rodriguez-Fraticelli fullname: Rodriguez-Fraticelli, Alejo organization: Department of Pediatrics, Harvard Medical School, Massachusetts, USA and Stem Cell Program, Boston Children's Hospital, Massachusetts, USA, United States – sequence: 13 givenname: Fernando surname: Camargo fullname: Camargo, Fernando organization: Stem Cell Program, Boston Children's Hospital, Massachusetts, USA and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, USA, United States – sequence: 14 givenname: Leïla surname: Perié fullname: Perié, Leïla organization: Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie, 75005 Paris, France, France – sequence: 15 givenname: Andreas surname: Trumpp fullname: Trumpp, Andreas organization: Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany and German Cancer Consortium (DKTK), 69120 Heidelberg, Germany, Germany – sequence: 16 givenname: Nina surname: Cabezas-Wallscheid fullname: Cabezas-Wallscheid, Nina organization: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany, Germany |
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| Title | 3032 – MOUSE MULTIPOTENT PROGENITOR 5 CELLS ARE LOCATED AT THE INTERPHASE BETWEEN HEMATOPOIETIC STEM AND PROGENITOR CELLS |
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