CD1d expression demarcates CDX4+ hemogenic mesoderm with definitive hematopoietic potential.

Autor:	Philip Creamer J; Department of Medicine, Division of Hematology, Washington University School of Medicine, St. Louis, MO, United States., Luff SA; Department of Medicine, Division of Hematology, Washington University School of Medicine, St. Louis, MO, United States; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai School of Medicine, New York, NY, United States., Yu H; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai School of Medicine, New York, NY, United States., Sturgeon CM; Department of Medicine, Division of Hematology, Washington University School of Medicine, St. Louis, MO, United States; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai School of Medicine, New York, NY, United States. Electronic address: christopher.sturgeon@mssm.edu.
Jazyk:	angličtina
Zdroj:	Stem cell research [Stem Cell Res] 2022 Jul; Vol. 62, pp. 102808. Date of Electronic Publication: 2022 May 08.
DOI:	10.1016/j.scr.2022.102808
Abstrakt:	To achieve efficient, reproducible differentiation of human pluripotent stem cells (hPSCs) towards specific hematopoietic cell-types, a comprehensive understanding of the necessary cell signaling and developmental trajectories involved is required. Previous studies have identified the mesodermal progenitors of extra-embryonic-like and intra-embryonic-like hemogenic endothelium (HE), via stage-specific WNT and ACTIVIN/NODAL, with GYPA/GYPB (CD235a/b) expression serving as a positive selection marker for mesoderm harboring exclusively extra-embryonic-like hemogenic potential. However, a positive mesodermal cell-surface marker with exclusively intra-embryonic-like hemogenic potential has not been identified. Recently, we reported that early mesodermal expression of CDX4 critically regulates definitive HE specification, suggesting that CDX4 may act in a cell-autonomous manner during hematopoietic development. To identify CDX4+ mesoderm, we performed single cell (sc)RNAseq on hPSC-derived mesodermal cultures, revealing CDX4 hi expressing mesodermal populations were uniquely enriched in the non-classical MHC-Class-1 receptor CD1D. Flow cytometry demonstrated approximately 60% of KDR+CD34-CD235a- mesoderm was CD1d+, and CDX4 was robustly enriched within CD1d+ mesoderm. Critically, only CD1d+ mesoderm harbored CD34+ HOXA+ HE with multilineage erythroid-myeloid-lymphoid potential. Thus, CDX4+CD1d+ expression within early mesoderm demarcates an early progenitor of HE. These insights may be used for further study of human hematopoietic development and improve hematopoietic differentiation conditions for regenerative medicine applications. (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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