Transcriptomics

Dataset Information

41

CXCL12/CXCR4 signaling enhances human PSC-derived hematopoietic progenitor function and overcomes early in vivo transplantation failure


ABSTRACT: Human pluripotent stem cells (hPSC) generate hematopoietic progenitor cells (HPC), but fail to engraft xenograft models, which is a hallmark feature of adult/somatic hematopoietic stem cells (HSC) from human donors. Progress to derive hPSC-derived HSCs has relied on cell autonomous approaches that force expression of transcription factors (TF), however the role of bone marrow (BM) niche remains poorly understood. Here, we quantified a failure of hPSC-HPCs to survive even in the first 24 h upon transplantation into the BM. Across several hPSC-HPC differentiation methodologies, we identified the lack of CXCR4 expression and network function. Ectopic CXCR4 conferred CXCL12-dependent signaling of hPSC-HPCs in biochemical assays and increased migration/chemotaxis and progenitor capacity, as well as survival and proliferation following transplantation in vivo. In addition, hPSC-HPCs forced to express CXCR4 demonstrated a transcriptional shift toward somatic HPCs, but this approach failed to produce long-term HSC engraftment. Our results reveal that independent of differentiation methods, networks involving CXCR4 should be targeted to generate HSCs with in vivo function from hPSCs. Overall design: Human pluripotent stem cell (hPSC) derived hematopoietic progenitor cells (HPC) were generated using previously described methods; Cytokines & BMP4 (Chadwick et al. Blood 2003) and endothelial-to-hematopoietic transition (EHT) (Lee et al. The Journal of Clinical Investigation 2017). Lentiviral was used to achieve CXCR4+ hPSC-HPCs, differentiated as previously described (Chadwick et al. Blood 2003). Adult/somatic HPCs were isolated from bone marrow, cord blood, and mobilized peripheral blood.

INSTRUMENT(S): [HG-U133A] Affymetrix Human Genome U133A Array

ORGANISM(S): Homo sapiens  

SUBMITTER: Mickie Bhatia  

PROVIDER: GSE106721 | GEO | 2018-06-21

REPOSITORIES: GEO

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Publications

CXCL12/CXCR4 Signaling Enhances Human PSC-Derived Hematopoietic Progenitor Function and Overcomes Early In Vivo Transplantation Failure.

Reid Jennifer C JC   Tanasijevic Borko B   Golubeva Diana D   Boyd Allison L AL   Porras Deanna P DP   Collins Tony J TJ   Bhatia Mickie M  

Stem cell reports 20180501 5


Human pluripotent stem cells (hPSCs) generate hematopoietic progenitor cells (HPCs) but fail to engraft xenograft models used to detect adult/somatic hematopoietic stem cells (HSCs) from donors. Recent progress to derive hPSC-derived HSCs has relied on cell-autonomous forced expression of transcription factors; however, the relationship of bone marrow to transplanted cells remains unknown. Here, we quantified a failure of hPSC-HPCs to survive even 24 hr post transplantation. Across several hPSC-  ...[more]

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