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Cell Rep. 2019 Jul 23;28(4):1063-1073.e5. doi: 10.1016/j.celrep.2019.06.084.

Integrin-α3 Is a Functional Marker of Ex Vivo Expanded Human Long-Term Hematopoietic Stem Cells.

Author information

1
Molecular Genetics of Stem Cells Laboratory, Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, H3T 1J4 QC, Canada.
2
Molecular Genetics of Stem Cells Laboratory, Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, H3T 1J4 QC, Canada; Division of Hematology, Maisonneuve-Rosemont Hospital, Montréal, H1T 2M4 QC, Canada; Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, H3T 1J4 QC, Canada. Electronic address: guy.sauvageau@umontreal.ca.

Abstract

Transplantation of expanded hematopoietic stem cells (HSCs) and gene therapy based on HSC engineering have emerged as promising approaches for the treatment of hematological diseases. Nevertheless, the immunophenotype of cultured HSCs remains poorly defined. Here, we identify Integrin-α3 (ITGA3) as a marker of cultured human HSCs. Exploiting the pyrimidoindole derivative UM171 to expand cord blood (CB) cells, we show that ITGA3 expression is sufficient to separate the primitive EPCR+CD90+CD133+CD34+CD45RA- HSC population into two functionally distinct fractions presenting mostly short-term (ITGA3-) and both short-term and long-term (ITGA3+) repopulating potential. ITGA3+ cells exhibit robust multilineage differentiation potential, serial reconstitution ability in immunocompromised mice, and an HSC-specific transcriptomic signature. Moreover, ITGA3 expression is functionally required for the long-term engraftment of CB cells. Altogether, our results indicate that ITGA3 is a reliable marker of cultured human long-term repopulating HSCs (LT-HSCs) and represents an important tool to improve the accuracy of prospective HSC identification in culture.

KEYWORDS:

HSC expansion; ITGA3; UM171

PMID:
31340144
DOI:
10.1016/j.celrep.2019.06.084
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