ID

45713

Description

Principal Investigator: Martin H. Steinberg, Boston University School of Medicine, Boston, MA, USA MeSH: Anemia, Sickle Cell,Fetal Hemoglobin https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001212 - Implement an efficient, highly reproducible and 'scalable' system for the production of large numbers of sickle cell anemia-specific iPS cells (iPSC). - Derive and characterize a novel, in vitro system for the production of an unlimited supply of erythroid lineage cells from the directed differentiation of 'clinical grade' transgene-free iPS cells; use this system to recapitulate erythroid-lineage ontogeny in vitro with the sequential development of primitive and definitive erythropoiesis, accompanied by the appropriate expression of stage-specific globin genes. - Identify developmental gene expression profile differences between erythroid precursors that produce primarily HbF and those that produce primarily HbA or HbS. - Determine the effects of the three known HbF major quantitative trait loci (QTL) on globin gene expression in disease-specific iPS cells during in vitro erythropoiesis. - Search for novel HbF genetic modifiers associated with markedly elevated HbF levels found in sickle cell anemia patients naturally, or in response to hydroxyurea treatment, by examining gene expression profiles and mRNA sequence of their iPSC-derived erythroid cells. - Develop and use a CRISPR-based gene editing platform to study the effect of novel HbF genetic modifiers, explore globin switching, and correct the HbS mutation in sickle iPSC lines.

Link

dbGaP-study=phs001212

Keywords

  1. 5/17/23 5/17/23 - Chiara Middel
Copyright Holder

Martin H. Steinberg, Boston University School of Medicine, Boston, MA, USA

Uploaded on

May 17, 2023

DOI

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License

Creative Commons BY 4.0

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dbGaP phs001212 NextGen Consortium: Globin Gene Expression in Sickle Cell Genotype-Specific iPS Cells

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