Dynamic activity of Erg promotes maturation of the hematopoietic system.
Abstract
Hematopoiesis changes over the lifetime to adapt to the physiology of development, maturation, and aging. Temporal changes in hematopoiesis parallel age-dependent incidences of certain blood diseases. Several heterochronic regulators of hematopoiesis have been identified, but how the master transcription factor (TF) circuitry of definitive hematopoietic stem cells (HSCs) adapts to changes in physiology over the lifespan is unknown. Here, we show that programmed upregulation of expression of the ETS family TF Erg during prenatal to adult maturation is evolutionarily conserved and required for implementation of adult patterns of HSC self-renewal and myeloid, erythroid, and lymphoid differentiation. Erg deficiency maintains fetal transcriptional and epigenetic programs in adulthood, and persistent juvenile phenotypes in Erg haploinsufficient mice are at least in part dependent on deregulation of the fetal-biased factor Hmga2. Overall, we identify a mechanism whereby master HSC TF networks are rewired to specify stage-specific hematopoiesis, a finding directly relevant to age-biased blood diseases.
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Research summary
The paper claims that the upregulation of the transcription factor Erg is essential for the maturation of hematopoietic stem cells and their differentiation patterns in adulthood. This research is relevant as it explores the mechanisms underlying hematopoiesis across the lifespan, which could provide insights into age-related blood diseases and the fundamental processes of aging.
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