Premature senescence impairs hematopoietic stem cell function during sickle cell disease in mice and humans.

Aditya Barve¹, Preeti Dabas¹, Adam Cornwell¹, Pramika Sriram¹, Alex Kopyov¹, Mattieu Zhai¹, Emilia Kooienga¹, Zakiya Kelley¹, James Johnson², Jacquelyn A Myers³, Esther A Obeng³, Guolian Kang⁴, Yunusa Olufadi⁴, Terri Cain¹, Lindsay Talbot⁵, David Spence^6,7, Mauricio Cortes⁸, Samuel A Miller⁸, Dirk Loeffler^1,9,10, Akshay Sharma¹¹, Shannon McKinney-Freeman^1,9

¹Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.

²WiCell Research Institute, Madison, WI, USA.

³Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.

⁴Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.

⁵Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN, USA.

⁶Department of Surgery, University of Tennessee Health Sciences Center, Memphis, TN, USA.

⁷Campbell Clinic, Germantown, TN, USA.

⁸Cellarity Inc., Somerville, MA, USA.

⁹Comprehensive Cancer Center, St. Jude Children's Research Hospital, Memphis, TN, USA.

¹⁰Department of Pathology and Laboratory Medicine, University of Tennessee, Memphis, TN, USA.

¹¹Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA.

PubMed DOI

Abstract

Sickle cell disease (SCD) is a blood disorder affecting millions worldwide. Emerging evidence reveals that SCD pathophysiology increases the risk of myeloid malignancies and hematopoietic stem cell (HSC) dysfunction, likely because of chronic stress on bone marrow. To investigate this further, we interrogated bone marrow hematopoietic stem and progenitor cells (HSPCs) from mice and individuals wit…

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