MEIS1 Regulates Hemogenic Endothelial Generation, Megakaryopoiesis, and Thrombopoiesis in Human Pluripotent Stem Cells by Targeting TAL1 and FLI1

Stem Cell Reports. 2018 Feb 13;10(2):447-460. doi: 10.1016/j.stemcr.2017.12.017. Epub 2018 Jan 18.

Abstract

Human pluripotent stem cells (hPSCs) provide an unlimited source for generating various kinds of functional blood cells. However, efficient strategies for generating large-scale functional blood cells from hPSCs are still lacking, and the mechanism underlying human hematopoiesis remains largely unknown. In this study, we identified myeloid ectopic viral integration site 1 homolog (MEIS1) as a crucial regulator of hPSC early hematopoietic differentiation. MEIS1 is vital for specification of APLNR+ mesoderm progenitors to functional hemogenic endothelial progenitors (HEPs), thereby controlling formation of hematopoietic progenitor cells (HPCs). TAL1 mediates the function of MEIS1 in HEP specification. In addition, MEIS1 is vital for megakaryopoiesis and thrombopoiesis from hPSCs. Mechanistically, FLI1 acts as a downstream gene necessary for the function of MEIS1 during megakaryopoiesis. Thus, MEIS1 controls human hematopoiesis in a stage-specific manner and can be potentially manipulated for large-scale generation of HPCs or platelets from hPSCs for therapeutic applications in regenerative medicine.

Keywords: FLI1; MEIS1; TAL1; hPSCs; hematopoiesis; hemogenic endothelial; megakaryopoiesis; thrombopoiesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apelin Receptors / genetics
  • Cell Differentiation / genetics
  • Gene Expression Regulation, Developmental / genetics
  • Hemangioblasts / cytology
  • Hemangioblasts / metabolism
  • Humans
  • Megakaryocytes / cytology
  • Megakaryocytes / metabolism
  • Myeloid Ecotropic Viral Integration Site 1 Protein / genetics*
  • Pluripotent Stem Cells*
  • Proto-Oncogene Protein c-fli-1 / genetics*
  • T-Cell Acute Lymphocytic Leukemia Protein 1 / genetics*
  • Thrombopoiesis / genetics*

Substances

  • APLNR protein, human
  • Apelin Receptors
  • FLI1 protein, human
  • MEIS1 protein, human
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Proto-Oncogene Protein c-fli-1
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • TAL1 protein, human