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

doi:10.1002/1873-3468.13621

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 journal › Article › peer-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 language	English
Pages (from-to)	3266-3287
Number of pages	22
Journal	FEBS Letters
Volume	593
Issue number	23
DOIs	https://doi.org/10.1002/1873-3468.13621
State	Published - 1 Dec 2019

Keywords

AFT024
coculture
hematopoietic stem cells
reprogramming
transcription factors

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10.1002/1873-3468.13621

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title = "Induction of human hemogenesis in adult fibroblasts by defined factors and hematopoietic coculture",

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.",

keywords = "AFT024, coculture, hematopoietic stem cells, reprogramming, transcription factors",

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

note = "Funding Information: The authors would like to thank the Sunita L. D{\textquoteright}Souza and the Pluripotent Stem Cell Core at the Icahn School of Medicine at Mount Sinai for helpful discussions and reagents. We also thank the flow cytometry shared resource Core as well as the Genomics Core Facility at ISMMS. KM was supported by NIH 5RO1HL119404 and NYSTEM C32597GG. MGD was supported by the grants 5RO1HL11904, 4R33AI116191‐031 (through BC), and F31 HL136148‐01. Publisher Copyright: {\textcopyright} 2019 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.",

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doi = "10.1002/1873-3468.13621",

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journal = "FEBS Letters",

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T1 - Induction of human hemogenesis in adult fibroblasts by defined factors and hematopoietic coculture

AU - Daniel, Michael G.

AU - Sachs, David

AU - Bernitz, Jeffrey M.

AU - Fstkchyan, Yesai

AU - Rapp, Katrina

AU - Satija, Namita

AU - Law, Kenneth

AU - Patel, Foram

AU - Gomes, Andreia M.

AU - Kim, Huen Suk

AU - Pereira, Carlos Filipe

AU - Chen, Benjamin

AU - Lemischka, Ihor R.

AU - Moore, Kateri A.

N1 - Funding Information: The authors would like to thank the Sunita L. D’Souza and the Pluripotent Stem Cell Core at the Icahn School of Medicine at Mount Sinai for helpful discussions and reagents. We also thank the flow cytometry shared resource Core as well as the Genomics Core Facility at ISMMS. KM was supported by NIH 5RO1HL119404 and NYSTEM C32597GG. MGD was supported by the grants 5RO1HL11904, 4R33AI116191‐031 (through BC), and F31 HL136148‐01. Publisher Copyright: © 2019 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

PY - 2019/12/1

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N2 - 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.

AB - 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.

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

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