美国纽约基因组中心Dan A. Landau研究组近日取得一项新成果,他们的最新工作表明,DNA甲基化的破坏改变了造血分化。2020年3月23日,国际知名学术期刊《自然—遗传学》在线发表了这一成果。
Title: DNA methylation disruption reshapes the hematopoietic differentiation landscape
Author: Franco Izzo, Stanley C. Lee, Asaf Poran, Ronan Chaligne, Federico Gaiti, Baptiste Gross, Rekha R. Murali, Sunil D. Deochand, Chelston Ang, Philippa Wyndham Jones, Anna S. Nam, Kyu-Tae Kim, Steven Kothen-Hill, Rafael C. Schulman, Michelle Ki, Priscillia Lhoumaud, Jane A. Skok, Aaron D. Viny, Ross L. Levine, Ephraim Kenigsberg, Omar Abdel-Wahab, Dan A. Landau
Issue&Volume: 2020-03-23
Abstract: Mutations in genes involved in DNA methylation (DNAme; for example, TET2 and DNMT3A) are frequently observed in hematological malignancies1,2,3 and clonal hematopoiesis4,5. Applying single-cell sequencing to murine hematopoietic stem and progenitor cells, we observed that these mutations disrupt hematopoietic differentiation, causing opposite shifts in the frequencies of erythroid versus myelomonocytic progenitors following Tet2 or Dnmt3a loss. Notably, these shifts trace back to transcriptional priming skews in uncommitted hematopoietic stem cells. To reconcile genome-wide DNAme changes with specific erythroid versus myelomonocytic skews, we provide evidence in support of differential sensitivity of transcription factors due to biases in CpG enrichment in their binding motif. Single-cell transcriptomes with targeted genotyping showed similar skews in transcriptional priming of DNMT3A-mutated human clonal hematopoiesis bone marrow progenitors. These data show that DNAme shapes the topography of hematopoietic differentiation, and support a model in which genome-wide methylation changes are transduced to differentiation skews through biases in CpG enrichment of the transcription factor binding motif.
DOI: 10.1038/s41588-020-0595-4
Source: https://www.nature.com/articles/s41588-020-0595-4
Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex
本期文章:《自然—遗传学》:Online/在线发表