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Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
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Progress and obstacles towards generating hematopoietic stem cells from pluripotent stem cells.

Jungmin Lee1, Brad Dykstra, Robert Sackstein

  • 1aDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge bProgram in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children's Hospital cDepartment of Dermatology, and Program of Excellence in Glycosciences, Brigham & Women's Hospital, Harvard Medical School dDivision of Hematology, Department of Medicine, Brigham & Women's Hospital eDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston fHarvard Stem Cell Institute, Cambridge, Massachusetts, USA *Jungmin Lee and Brad Dykstra contributed equally to the writing of this manuscript.

Current Opinion in Hematology
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Generating transplantable hematopoietic stem cells (HSCs) from human pluripotent stem cells (PSCs) shows promise. While progress has been made, achieving robust HSCs for transplantation requires further understanding of regulatory pathways and supportive conditions.

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Area of Science:

  • Stem cell biology
  • Hematopoiesis
  • Regenerative medicine

Background:

  • Human pluripotent stem cells (PSCs) offer a potential source for hematopoietic stem cells (HSCs).
  • HSCs are crucial for disease modeling and clinical applications like transplantation.
  • Deriving definitive HSCs from PSCs remains a significant challenge.

Purpose of the Study:

  • To review the current status of HSC derivation from PSCs.
  • To highlight existing challenges and obstacles in the field.
  • To propose future directions for achieving robust HSC generation.

Main Methods:

  • Review of recent scientific literature on PSC-derived HSCs.
  • Analysis of developmental intermediates and supporting factors.
  • Evaluation of strategies for recapitulating niche-like conditions.

Main Results:

  • Advancements include derivation of developmental intermediates.
  • Identification of key transcription factors and small molecules.
  • Development of strategies to mimic niche conditions for hematopoiesis.

Conclusions:

  • Progress in generating hematopoietic progenitor cells from PSCs is notable.
  • Generation of transplantable HSCs from PSCs is still elusive.
  • Further research into regulatory pathways, supportive conditions, and homing properties is needed.