Combination of CD49b and CD229 Reveals a Subset of Multipotent Progenitors With Short-Term Activity Within the Hematopoietic Stem Cell Compartment

Author:

Somuncular Ece1,Su Tsu-Yi1ORCID,Dumral Özge1,Johansson Anne-Sofie1ORCID,Luc Sidinh1ORCID

Affiliation:

1. Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital , Stockholm , Sweden

Abstract

Abstract Hematopoiesis is maintained by hematopoietic stem cells (HSCs) that replenish all blood lineages throughout life. It is well-established that the HSC pool is functionally heterogeneous consisting of cells differing in longevity, self-renewal ability, cell proliferation, and lineage differentiation. Although HSCs can be identified through the Lineage–Sca-1+c-Kit+CD48–CD34–CD150+ immunophenotype, the cell surface marker combination does not permit absolute purification of functional HSCs with long-term reconstituting ability. Therefore, prospective isolation of long-term HSCs is crucial for mechanistic understanding of the biological functions of HSCs and for resolving functional heterogeneity within the HSC population. Here, we show that the combination of CD229 and CD49b cell surface markers within the phenotypic HSC compartment identifies a subset of multipotent progenitor (MPP) cells with high proliferative activity and short-term reconstituting ability. Thus, the addition of CD229 and CD49b to conventional HSC markers permits prospective isolation of functional HSCs by distinguishing MPPs in the HSC compartment.

Funder

Wallenberg Academy Fellow

Swedish Childhood Cancer Fund

European Hematology Association

Cancerfonden

Vetenskapsrådet

Stem cell and Regenerative Medicine

Åke Olsson foundation

Åke Wiberg foundation

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,General Medicine

Reference23 articles.

1. Hematopoiesis: an evolving paradigm for stem cell biology;Orkin,2008

2. Haematopoietic stem cell self-renewal in vivo and ex vivo;Wilkinson,2020

3. Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells;Carrelha,2018

4. Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy;Sanjuan-Pla,2013

5. Clonal analysis unveils self-renewing lineage-restricted progenitors generated directly from hematopoietic stem cells;Yamamoto,2013

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