Deciphering the hierarchy of angiohematopoietic progenitors from human pluripotent stem cells

Abstract

Identification of sequential progenitors leading to blood formation from pluripotent stem cells (PSCs) will be essential for understanding the molecular mechanisms of hematopoietic lineage specification and for development of technologies for in vitro production of hematopoietic stem cells (HSCs). It is well established that during development, blood and endothelial cells in the extraembryonic and embryonic compartments are formed in parallel from precursors with angiogenic and hematopoietic potentials. However, the identity and hierarchy of these precursors in human PSC (hPSC) cultures remain obscure. Using developmental stage-specific mesodermal and endothelial markers and functional assays, we recently identified discrete populations of angiohematopoietic progenitors from hPSCs, including mesodermal precursors and hemogenic endothelial cells with primitive and definitive hematopoietic potentials. In addition, we discovered a novel population of multipotent hematopoietic progenitors with an erythroid phenotype, which retain angiogenic potential. Here we introduce our recent findings and discuss their implication for defining putative HSC precursor and factors required for activation of self-renewal potential in hematopoietic cells emerging from endothelium.

Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy

“…1b). Similar to previous reports 3,4,15 , we found that CD34 + cells from day 10 embryoid bodies expressed the highest levels of key transcription factors for lymphoid differentiation (Supplementary Fig. 4a), specifically showing increased expression of Notch 1 and CD127 (IL7Rα) in the CD34 + CD43 − subset compared to CD34 − CD43 − cells (Supplementary Fig.…”

Skin, fascias, and scars: symptoms and systemic connections

“…The dermis originates in the mesoderm, where, among other things, the connective tissue, bone, cartilage, blood, and their relevant organs are found 10–12. The dermis supports the epidermis and nourishes it 13.…”

Hematopoietic specification from human pluripotent stem cells: current advances and challenges toward de novo generation of hematopoietic stem cells

“…77 Because these markers could also be found on differentiated cells at postmesodermal stages, we demarcated mesodermal stage of development as EMH lin 2 , ie, the stage at which cells lack the expression of endothelial (CD31, VE-cadherin), endothelial/mesenchymal (CD73, CD105), and hematopoietic (CD43, CD45) lineage markers. 86,90 On the basis of these analyses, we identified 2 distinct phases of mesodermal development.…”

“…The developmental progression from HE to hematopoietic progenitors depends on transforming growth factor beta (TGFb) signaling. In an embryoid body differentiation system, treatment of hESCs at the CD31 86,90 Although AHPs expressed the erythroid cell marker CD235a, they had a unique potential to form a broad spectrum of hematopoietic colonies in serum-free medium supplemented with hematopoietic cytokines and FGF2. 86 Gross morphologic examinations of some of these colonies resemble hemangioblast/BL colonies formed by BL-CFCs.…”