The Cell Type-Specific 5hmC Landscape and Dynamics of Healthy Human Hematopoiesis and TET2-Mutant Preleukemia.
Yusuke NakauchiArmon AziziDaniel ThomasM Ryan CorcesAndreas ReinischRajiv SharmaDavid Cruz HernandezThomas KöhnkeDaiki KariganeAmy C FanDaniel Martinez-KramsMelissa StaffordSatinder KaurRitika DuttaPaul PhanAsiri Saumya EdiriwickremaErin McCarthyYuhong NingTierney PhillipsChristopher K EllisonGulfem D GulerAnna BergamaschiChin-Jen KuSamuel LevyRavindra MajetiPublished in: Blood cancer discovery (2022)
We show that 5-hydroxymethylation profiles are cell type-specific and associated with transcriptional abundance and chromatin accessibility across human hematopoiesis. TET2 loss caused aberrant growth and differentiation phenotypes and disrupted 5hmC and transcriptional landscapes. Treatment of TET2 KO HSPCs with ascorbate or azacitidine reverted 5hmC profiles and restored aberrant phenotypes. This article is highlighted in the In This Issue feature, p. 265.