Haematopoietic stem and progenitor cells from human pluripotent stem cells

Nature. 2017 May 25;545(7655):432-438. doi: 10.1038/nature22370. Epub 2017 May 17.

Abstract

A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are sufficient to convert haemogenic endothelium into haematopoietic stem and progenitor cells that engraft myeloid, B and T cells in primary and secondary mouse recipients. Our combined approach of morphogen-driven differentiation and transcription-factor-mediated cell fate conversion produces haematopoietic stem and progenitor cells from pluripotent stem cells and holds promise for modelling haematopoietic disease in humanized mice and for therapeutic strategies in genetic blood disorders.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Lineage*
  • Cellular Reprogramming
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Endothelium / cytology
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism*
  • Homeobox A10 Proteins
  • Homeodomain Proteins / metabolism
  • Humans
  • Mice
  • Pluripotent Stem Cells / cytology*
  • Proto-Oncogene Proteins / metabolism
  • Repressor Proteins / metabolism
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism*
  • Transcriptional Regulator ERG / metabolism

Substances

  • Core Binding Factor Alpha 2 Subunit
  • ERG protein, human
  • HOXA5 protein, human
  • Homeobox A10 Proteins
  • Homeodomain Proteins
  • LCOR protein, human
  • Proto-Oncogene Proteins
  • RUNX1 protein, human
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Regulator ERG
  • homeobox protein HOXA9
  • proto-oncogene protein Spi-1
  • HOXA10 protein, human