Physiological and Aberrant γ-Globin Transcription During Development

Abstract

The expression of the fetal Gγ- and Aγ-globin genes in normal development is confined to the fetal period, where two γ-globin chains assemble with two α-globin chains to form α2γ2 tetramers (HbF). HbF sustains oxygen delivery to tissues until birth, when β-globin replaces γ-globin, leading to the formation of α2β2 tetramers (HbA). However, in different benign and pathological conditions, HbF is expressed in adult cells, as it happens in the hereditary persistence of fetal hemoglobin, in anemias and in some leukemias. The molecular basis of γ-globin differential expression in the fetus and of its inappropriate activation in adult cells is largely unknown, although in recent years, a few transcription factors involved in this process have been identified. The recent discovery that fetal cells can persist to adulthood and contribute to disease raises the possibility that postnatal γ-globin expression could, in some cases, represent the signature of the fetal cellular origin.

A mass spectrometry assay for detection of endogenous and lentiviral engineered hemoglobin in cultured cells and sickle cell disease mice

“…7,8 The disease manifests gradually over the first months of age, as fetal hemoglobin (HbF, α 2 γ 2 ) is replaced by HbS. 7,8 Despite current advances in therapy for SCD, patients still experience significant end organ damage and decreased lifespan. 7,9 Common newborn screening methods include the electrophoretic method introduced in 1949 10 and high-performance liquid chromatography (HPLC).…”

“…Complications of SCD include infection and vaso‐occlusive events including pain crises and acute chest syndrome 7,8 . The disease manifests gradually over the first months of age, as fetal hemoglobin (HbF, α 2 γ 2 ) is replaced by HbS 7,8 . Despite current advances in therapy for SCD, patients still experience significant end organ damage and decreased lifespan 7,9 .…”

“…These changes result in a multitude of pathophysiologic complications including inflammation, ischemia and anemia 6 . Complications of SCD include infection and vaso‐occlusive events including pain crises and acute chest syndrome 7,8 . The disease manifests gradually over the first months of age, as fetal hemoglobin (HbF, α 2 γ 2 ) is replaced by HbS 7,8 .…”

A Journey Into the Unknown: PhD Students in a European Training Network on Age-related Changes in Hematopoiesis Conduct Their Project During a Global Pandemic

“…Some of us started on this project during or after the first lockdown, causing further delays, which led to a multiphasic pattern of recruitment (Figure 1). During the first lockdown, we individually set up our strategies to progress our research projects at home by either reading scientific literature, writing review papers, [6][7][8][9] or planning experiments for when we would eventually return to work. By summer 2020, many of us began to slowly get back to the laboratory in shifts or for a limited time to avoid overcrowding of spaces.…”