A complex interaction of different processes play a critical role in the development of hematopoietic lineages, and among the most important are the controls of hematopoietic stem cell (HSC) commitment. Understanding this process is critical to understanding HSC function as well as self-renewal, and this understanding will lead to novel insights into manipulation of HSC for therapeutic purposes, as well as understanding disease processes which involve HSC, including leukemia. Finally, advances in understanding HSC commitment will serve as a model for understanding other types of stem cells. This program, """"""""Hematopoietic Stem Cell Commitment,"""""""" consists of 4 projects, all of which are interrelated and focused on understanding some aspect of HSC regulation and function. They include: Project 1: """"""""Branching points of hematopoietic stem cell commitment"""""""", (Project Leader: Koichi Akashi, Dana Farber Cancer Institute, Harvard Medical School; Project 2, """"""""Signal Transduction Mechanisms in Hematopoietic Stem Cells"""""""" (Project Leader: Roger J. Davis, University of Massachusetts Medical Center, Worcester); Project 3: """"""""Runx1 in hematopoietic stem cells"""""""" (Project Leader: Dong-Er Zhang, Scripps Research Institute); and Project 4, """"""""Regulation of C/EBP alpha in hematopoiesis"""""""" (Project Leader: Daniel G. Tenen, Beth Israel Deaconess Medical Center, Harvard Medical School). The administrative core will be responsible for many interactive functions of the program, including regular meetings, seminars, and communication among projects. A Biostatistics Core will provide direction with statistical design and analysis. ? ?

Public Health Relevance

By combining a variety of approaches, including studies of transcriptional regulation, signal transduction, and knockout and knockin mice, we will provide valuable new information concerning the regulation of stem cell function. ? ? ? ? ?

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Program Projects (P01)
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Special Emphasis Panel (ZDK1-GRB-R (J1))
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Wright, Daniel G
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Beth Israel Deaconess Medical Center
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Li, A; Jiao, Y; Yong, K J et al. (2015) SALL4 is a new target in endometrial cancer. Oncogene 34:63-72
Komeno, Yukiko; Huang, Yi-Jou; Qiu, Jinsong et al. (2015) SRSF2 Is Essential for Hematopoiesis, and Its Myelodysplastic Syndrome-Related Mutations Dysregulate Alternative Pre-mRNA Splicing. Mol Cell Biol 35:3071-82
Lam, Kentson; Muselman, Alexander; Du, Randal et al. (2014) Hmga2 is a direct target gene of RUNX1 and regulates expansion of myeloid progenitors in mice. Blood 124:2203-12
Komeno, Yukiko; Yan, Ming; Matsuura, Shinobu et al. (2014) Runx1 exon 6-related alternative splicing isoforms differentially regulate hematopoiesis in mice. Blood 123:3760-9
Ueno, Shikiko; Lu, Jiayun; He, Jie et al. (2014) Aberrant expression of SALL4 in acute B cell lymphoblastic leukemia: mechanism, function, and implication for a potential novel therapeutic target. Exp Hematol 42:307-316.e8
Welner, Robert S; Bararia, Deepak; Amabile, Giovanni et al. (2013) C/EBP? is required for development of dendritic cell progenitors. Blood 121:4073-81
Yong, Kol Jia; Gao, Chong; Lim, Joline S J et al. (2013) Oncofetal gene SALL4 in aggressive hepatocellular carcinoma. N Engl J Med 368:2266-76
Li, Ailing; Yang, Youyang; Gao, Chong et al. (2013) A SALL4/MLL/HOXA9 pathway in murine and human myeloid leukemogenesis. J Clin Invest 123:4195-207
Gao, Chong; Kong, Nikki R; Li, Ailing et al. (2013) SALL4 is a key transcription regulator in normal human hematopoiesis. Transfusion 53:1037-49
Gao, Chong; Dimitrov, Todor; Yong, Kol Jia et al. (2013) Targeting transcription factor SALL4 in acute myeloid leukemia by interrupting its interaction with an epigenetic complex. Blood 121:1413-21

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