GPI-80 defines self-renewal ability in hematopoietic stem cells during human development

Sacha Leandra Prashad; Vincenzo Calvanese; Catherine Yao Yao; Joshua Kaiser; Yanling Wang; Rajkumar Sasidharan; Gay Crooks; Mattias Magnusson; Hanna Katri Annikki Mikkola

doi:10.1016/j.stem.2014.10.020

GPI-80 defines self-renewal ability in hematopoietic stem cells during human development

Cell Stem Cell. 2015 Jan 8;16(1):80-7. doi: 10.1016/j.stem.2014.10.020. Epub 2014 Nov 13.

Authors

Sacha Leandra Prashad¹, Vincenzo Calvanese², Catherine Yao Yao², Joshua Kaiser², Yanling Wang³, Rajkumar Sasidharan², Gay Crooks⁴, Mattias Magnusson², Hanna Katri Annikki Mikkola⁵

Affiliations

¹ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁴ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁵ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: hmikkola@mcdb.ucla.edu.

Abstract

Advances in pluripotent stem cell and reprogramming technologies have given us the hope of generating hematopoietic stem cells (HSCs) in culture. To succeed, greater understanding of the self-renewing HSC during human development is required. We discovered that the glycophosphatidylinositol-anchored surface protein GPI-80 defines a subpopulation of human fetal liver hematopoietic stem/progenitor cells (HSPCs) with self-renewal ability. CD34(+)CD38(lo/-)CD90(+)GPI-80(+) HSPCs were the sole population that maintained proliferative potential and an undifferentiated state in stroma coculture and engrafted in immunodeficient mice. GPI-80 expression also enabled tracking of HSPCs once they emerged from endothelium and migrated between human fetal hematopoietic niches. GPI-80 colocalized on the surface of HSPCs with Integrin alpha-M (ITGAM), which in leukocytes cooperates with GPI-80 to support migration. Knockdown of GPI-80 or ITGAM was sufficient to compromise HSPC expansion in culture and engraftment in vivo. These findings indicate that human fetal HSCs employ mechanisms used in leukocyte adhesion and migration to mediate HSC self-renewal.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Amidohydrolases / metabolism*
CD11b Antigen / metabolism
Cell Adhesion Molecules / metabolism*
Cell Differentiation
Cell Lineage
Cell Proliferation
Embryonic Development*
Fetus / cytology
Flow Cytometry
GPI-Linked Proteins / metabolism
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells / cytology*
Hematopoietic Stem Cells / metabolism*
Humans
Immunophenotyping
Liver / cytology
Liver / embryology

Substances

CD11b Antigen
Cell Adhesion Molecules
GPI-Linked Proteins
ITGAM protein, human
Amidohydrolases
VNN2 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding