Peer-Reviewed Publication
Nat Genet2026September 15, 2026Journal Article
Type 1 interferon perturbates clonal competition by reshaping human blood development.
Chhiring Lama1, Danielle Isakov1,2, Shira Rosenberg1, Miguel Quijada-Álamo3, Mirca S Saurty-Seerunghen1, Sara Moein1, Mathis Nozais1, Tsega-Ab Abera1, Olivia Sakaguchi1, Mansi Totwani1, Grace Freed3, Leila Zaydon1, Chi-Lam Poon4, Neelang Parghi1, Andrea Kubas-Meyer1, Amy X Xie5,6, Mohamed Omar7, Daniel Choi8, Franco Castillo-Tokumori8, Ghaith Abu-Zeinah8, Alicia Dillard1, Saravanan Ganesan8,9, Nathaniel D Omans8,9,10, Neville Dusaj2,8,9, Paulina Chamely8,9, Eleni Mimitou11, Peter Smibert12, Heidi E Kosiorek13, Amylou C Dueck14, Rona Weinberg15, Ronan Chaligne6, Bridget Marcellino16,17, Luigi Marchionni1, Sanjay Patel1, Paul Simonson1, Dan A Landau8,9,10,18, Elvin Wagenblast3, Ronald Hoffman15,17, Anna S Nam19,20,21,22
1Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
2Tri-Institutional MD-PhD Program, Weill Cornell Medicine, Rockefeller University, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
3Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
4Department of Physiology, Biophysics & Systems Biology, Weill Cornell Medicine, New York, NY, USA.
5Biochemistry, Structural Biology, Cell Biology, Developmental Biology and Molecular Biology Graduate Programs, Weill Cornell Medicine, New York, NY, USA.
6Computational Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
7Department of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
8Division of Hematology and Medical Oncology, Department of Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
9New York Genome Center, New York, NY, USA.
10Tri-Institutional Training Program in Computational Biology and Medicine, Memorial Sloan Kettering Cancer Center, Cornell University, Weill Cornell Medicine, New York, NY, USA.
11Immunai, New York, NY, USA.
1210x Genomics, Pleasanton, CA, USA.
13Department of Biostatistics, Mayo Clinic Arizona, Scottsdale, AZ, USA.
14Department of Quantitative Health Sciences and Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN, USA.
15New York Blood Center, New York, NY, USA.
16Myeloproliferative Neoplasms Research Consortium, New York, NY, USA.
17Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
18Sandra and Edward Meyer Cancer Center, New York, NY, USA.
19Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. shn9035@med.cornell.edu.
20Biochemistry, Structural Biology, Cell Biology, Developmental Biology and Molecular Biology Graduate Programs, Weill Cornell Medicine, New York, NY, USA. shn9035@med.cornell.edu.
21Tri-Institutional Training Program in Computational Biology and Medicine, Memorial Sloan Kettering Cancer Center, Cornell University, Weill Cornell Medicine, New York, NY, USA. shn9035@med.cornell.edu.
22Sandra and Edward Meyer Cancer Center, New York, NY, USA. shn9035@med.cornell.edu.
Abstract
Inflammation accelerates evolutionary dynamics of hematopoietic stem cells (HSCs) in clonal hematopoiesis and myeloid neoplasms. We studied HSCs, progenitors and immune cells from patients with myeloproliferative neoplasms at baseline and following interferon-α (IFNα) treatment, the only therapy to deplete mutated stem cells. We deployed single-cell multiomics methods that distinguish the IFNα eff…
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