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Respecifying human iPSC-derived blood cells into highly engraftable hematopoietic stem and progenitor cells with a single factor.

Derivation of human hematopoietic stem cells (HSCs) from induced pluripotent stem cells (iPSCs) offers considerable promise for cell therapy, disease modeling, and drug screening. However, efficient derivation of functional iPSC-derived HSCs with in vivo engraftability and multilineage potential rem... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America February 27, 2018, Vol.115(9), pp.2180-2185
Main Author: Tan, Yu-Ting
Other Authors: Ye, Lin , Xie, Fei , Beyer, Ashley I , Muench, Marcus O , Wang, Jiaming , Chen, Zhu , Liu, Han , Chen, Sai-Juan , Kan, Yuet Wai
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1718446115
Link: http://search.proquest.com/docview/1993382653/?pq-origsite=primo
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title: Respecifying human iPSC-derived blood cells into highly engraftable hematopoietic stem and progenitor cells with a single factor.
format: Article
creator:
  • Tan, Yu-Ting
  • Ye, Lin
  • Xie, Fei
  • Beyer, Ashley I
  • Muench, Marcus O
  • Wang, Jiaming
  • Chen, Zhu
  • Liu, Han
  • Chen, Sai-Juan
  • Kan, Yuet Wai
subjects:
  • Animals–Physiology
  • Cell Differentiation–Physiology
  • Erythroid Cells–Drug Effects
  • Gene Expression Regulation–Genetics
  • Hematopoietic Stem Cells–Metabolism
  • Humans–Genetics
  • Induced Pluripotent Stem Cells–Metabolism
  • Mice–Metabolism
  • Myeloid-Lymphoid Leukemia Protein–Metabolism
  • Oncogene Proteins, Fusion–Metabolism
  • Teratoma–Metabolism
  • Mll-Af4 Fusion Protein, Human
  • Oncogene Proteins, Fusion
  • Myeloid-Lymphoid Leukemia Protein
  • Mll-Af4
  • Engraftability
  • Hematopoietic Stem Cells
  • Human Induced Pluripotent Stem Cells
  • Leukemia
ispartof: Proceedings of the National Academy of Sciences of the United States of America, February 27, 2018, Vol.115(9), pp.2180-2185
description: Derivation of human hematopoietic stem cells (HSCs) from induced pluripotent stem cells (iPSCs) offers considerable promise for cell therapy, disease modeling, and drug screening. However, efficient derivation of functional iPSC-derived HSCs with in vivo engraftability and multilineage potential remains challenging. Here, we demonstrate a tractable approach for respecifying iPSC-derived blood cells into highly engraftable hematopoietic stem and progenitor cells (HSPCs) through transient expression of a single transcription factor, MLL-AF4. These induced HSPCs (iHSPCs) derived from iPSCs are able to fully reconstitute the human hematopoietic system in the recipient mice without myeloid bias. iHSPCs are long-term engraftable, but they are also prone to leukemic transformation during the long-term engraftment period. On the contrary, primary HSPCs with the same induction sustain the long-term engraftment without leukemic transformation. These findings demonstrate the feasibility of activating...
language: eng
source:
identifier: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1718446115
fulltext: fulltext
issn:
  • 10916490
  • 1091-6490
url: Link


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titleRespecifying human iPSC-derived blood cells into highly engraftable hematopoietic stem and progenitor cells with a single factor.
creatorTan, Yu-Ting ; Ye, Lin ; Xie, Fei ; Beyer, Ashley I ; Muench, Marcus O ; Wang, Jiaming ; Chen, Zhu ; Liu, Han ; Chen, Sai-Juan ; Kan, Yuet Wai
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ispartofProceedings of the National Academy of Sciences of the United States of America, February 27, 2018, Vol.115(9), pp.2180-2185
identifierE-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1718446115
subjectAnimals–Physiology ; Cell Differentiation–Physiology ; Erythroid Cells–Drug Effects ; Gene Expression Regulation–Genetics ; Hematopoietic Stem Cells–Metabolism ; Humans–Genetics ; Induced Pluripotent Stem Cells–Metabolism ; Mice–Metabolism ; Myeloid-Lymphoid Leukemia Protein–Metabolism ; Oncogene Proteins, Fusion–Metabolism ; Teratoma–Metabolism ; Mll-Af4 Fusion Protein, Human ; Oncogene Proteins, Fusion ; Myeloid-Lymphoid Leukemia Protein ; Mll-Af4 ; Engraftability ; Hematopoietic Stem Cells ; Human Induced Pluripotent Stem Cells ; Leukemia
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descriptionDerivation of human hematopoietic stem cells (HSCs) from induced pluripotent stem cells (iPSCs) offers considerable promise for cell therapy, disease modeling, and drug screening. However, efficient derivation of functional iPSC-derived HSCs with in vivo engraftability and multilineage potential remains challenging. Here, we demonstrate a tractable approach for respecifying iPSC-derived blood cells into highly engraftable hematopoietic stem and progenitor cells (HSPCs) through transient expression of a single transcription factor, MLL-AF4. These induced HSPCs (iHSPCs) derived from iPSCs are able to fully reconstitute the human hematopoietic system in the recipient mice without myeloid bias. iHSPCs are long-term engraftable, but they are also prone to leukemic transformation during the long-term engraftment period. On the contrary, primary HSPCs with the same induction sustain the long-term engraftment without leukemic transformation. These findings demonstrate the feasibility of activating...
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