Induction of human hemogenesis in adult fibroblasts by defined factors and hematopoietic coculture

Michael G. Daniel, David Sachs, Jeffrey M. Bernitz, Yesai Fstkchyan, Katrina Rapp, Namita Satija, Kenneth Law, Foram Patel, Andreia M. Gomes, Huen Suk Kim, Carlos Filipe Pereira, Benjamin Chen, Ihor R. Lemischka, Kateri A. Moore

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Transcription factor (TF)-based reprogramming of somatic tissues holds great promise for regenerative medicine. Previously, we demonstrated that the TFs GATA2, GFI1B, and FOS convert mouse and human fibroblasts to hemogenic endothelial-like precursors that generate hematopoietic stem progenitor (HSPC)-like cells over time. This conversion is lacking in robustness both in yield and biological function. Herein, we show that inclusion of GFI1 to the reprogramming cocktail significantly expands the HSPC-like population. AFT024 coculture imparts functional potential to these cells and allows quantification of stem cell frequency. Altogether, we demonstrate an improved human hemogenic induction protocol that could provide a valuable human in vitro model of hematopoiesis for disease modeling and a platform for cell-based therapeutics. Database: Gene expression data are available in the Gene Expression Omnibus (GEO) database under the accession number GSE130361.

Original languageEnglish
Pages (from-to)3266-3287
Number of pages22
JournalFEBS Letters
Volume593
Issue number23
DOIs
StatePublished - 1 Dec 2019

Keywords

  • AFT024
  • coculture
  • hematopoietic stem cells
  • reprogramming
  • transcription factors

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