CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation
Authors: Alireza Ghamari
Nancy A Speck
Xiongwei Cai
Kai Tan
Richard A Young
Anne L Robertson
Alan B Cantor
Hsuan-Ting Huang
Eirini Trompouki
Yan Li
Vy Nguyen
Iwo Kucinski
Song Yang
Brian J Abraham
Peng Gao
Joanna Tober
Iannis Aifantis
P Paul Liu
Michael Superdock
Nicola K Wilson
Leonard I Zon
Katie L Kathrein
Chung-Tsai Lee
Yalin Guo
Jingmei Hsu
Fernando J Calero-Nieto
Ellen M Durand
Jing Jiang
Scott A Gerber
Yi Zhou
Wei Tong
Long Gao
R Katherine Hyde
Victoria Moignard
Shuqian Yu
Avik Choudhuri
Berthold G√∂ttgens
Journal: Proceedings of the National Academy of Sciences of the United States of America (2020)
Discipline: Multidisciplinary
Keywords: CHD7; RUNX1; hematopoiesis.
Affiliations: Division of Hematology/Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104., Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104., Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104., Stem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115., Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138., Cambridge Institute for Medical Research, Department of Haematology, Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom CB2 OXY., Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142., National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892., Department of Microbiology and Immunology, Geisel School of Medicine, Lebanon, NH 03756., Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115., Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, PA 19104., Division of Oncology and Center for Childhood Cancer Research, Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA 19104., Department of Pathology and Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016., Department of Genetics, Geisel School of Medicine, Lebanon, NH 03756., Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104., Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104;  ., Stem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115;  .

Abstract:  Hematopoietic stem and progenitor cell (HSPC) formation and lineage differentiation involve gene expression programs orchestrated by transcription factors and epigenetic regulators. Genetic disruption of the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7) expanded phenotypic HSPCs, erythroid, and myeloid lineages in zebrafish and mouse embryos. CHD7 acts to suppress hematopoietic differentiation. Binding motifs for RUNX and other hematopoietic transcription factors are enriched at sites occupied by CHD7, and decreased RUNX1 occupancy correlated with loss of CHD7 localization. CHD7 physically interacts with RUNX1 and suppresses RUNX1-induced expansion of HSPCs during development through modulation of RUNX1 activity. Consequently, the RUNX1:CHD7 axis provides proper timing and function of HSPCs as they emerge during hematopoietic development or mature in adults, representing a distinct and evolutionarily conserved control mechanism to ensure accurate hematopoietic lineage differentiation. 

Retracted: No

PubPeer comments:
 An image and figure 4(a) appears to overlap with an image in figure 5(a). Could the authors please review and comment? ***  *** Full figures  ***  , 
 I agree with the concerns shared in comments #1. Some additional similarities between panels in Figures 4 and 5. Boxes of the same color highlight areas that look similar. The similarity pointed out above in #1 is marked with red boxes.  Could the authors please clarify if these are the same experiments? The labels appear to suggest these are different samples. , 
 Upon closer inspection these are not simple similarities, as those expected if the same photo was inserted twice by accident. There are some differences between the panels as well. Here are the pairs of panels marked above with pink and yellow boxes, respectively in zoomed-in view. I have marked areas that look different between the photos with thin ellipses and circles.   , 
 #3 Dear Elisabeth, Thank you for the comment. We are checking the data and will contact the journal for advice. Best regards! Jie Yan , 
 It has been about a year since the authors responded. On 9 15 21, I contacted the journal to alert them to these concerns. , 
 We have contacted the magazine for a long time and provided the corrected original pictures, which are currently in the process of corrigendum. ,