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CD1d expression demarcates CDX4+ hemogenic mesoderm with definitive hematopoietic potential.
- Source :
-
Stem cell research [Stem Cell Res] 2022 Jul; Vol. 62, pp. 102808. Date of Electronic Publication: 2022 May 08. - Publication Year :
- 2022
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Abstract
- 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 <superscript>hi</superscript> 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.<br /> (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Antigens, CD1d metabolism
Antigens, CD34 metabolism
Cell Differentiation physiology
Glycophorins metabolism
Hematopoiesis physiology
Hematopoietic Stem Cells metabolism
Homeodomain Proteins genetics
Homeodomain Proteins metabolism
Humans
Mesoderm metabolism
Hemangioblasts metabolism
Pluripotent Stem Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1876-7753
- Volume :
- 62
- Database :
- MEDLINE
- Journal :
- Stem cell research
- Publication Type :
- Academic Journal
- Accession number :
- 35569347
- Full Text :
- https://doi.org/10.1016/j.scr.2022.102808