Direct evidence for interaction between human erythroid progenitor cells and a hemoglobin switching activity present in fetal sheep serum.

Stamatoyannopoulos, George; Nakamoto, Betty; Kurachi, Sumiko; Papayannopoulou, T

doi:10.1073/pnas.80.18.5650

Cited by 19 publications

(3 citation statements)

References 19 publications

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“…A provocative implication from these studies is that globin gene regulatory programs reside in erythroid progenitors. Indeed, Papayonnopoulou and collaborators provide early evidence of this phenomenon, and imply that a minority of “pre-programmed” adult erythroid progenitors give rise to erythroblasts expressing HbF (67, 68). Therefore, the most effective pharmacologic agents might exploit the regulatory mechanisms in erythroid progenitors to either enrich this small population of “HbF programmed cells” or override γ-globin silencing in the majority of BFU-Es engaged with adult globin expression regulatory factors (Figure 2C).…”

Section: Erythroid Progenitors As a Target For Treating Disordered Ermentioning

confidence: 99%

Characterization, regulation, and targeting of erythroid progenitors in normal and disordered human erythropoiesis

Dulmovits

Hom

Narla

et al. 2017

Current Opinion in Hematology

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Purpose of review The erythroid progenitors BFU-E (burst-forming unit-erythroid) and CFU-E (colony-forming unit-erythroid) have a critical role in erythropoiesis. They represent a heterogeneous and poorly characterized population of cells with modifiable self-renewal, proliferation and differentiation capabilities. This review focuses on the current state of erythroid progenitor biology with regard to immunophenotypic identification and regulatory programs; in addition, we will discuss the therapeutic implications of using these erythroid progenitors as pharmacologic targets. Recent findings Erythroid progenitors are classically defined by the appearance of morphologically defined colonies in semisolid cultures. However, these prior systems preclude a more thorough understanding of the composite nature of progenitor populations. Recent studies employing novel flow cytometric and cell-based assays have helped to redefine hematopoiesis, and suggest that erythroid progenitors may arise from different levels of the hematopoietic tree. Moreover, the identification of cell surface marker patterns in human BFU-E and CFU-E enhance our ability to perform downstream functional and molecular analyses at the population and single cell level. Advances in these techniques have already revealed novel subpopulations with increased self-renewing capacity, roles for erythroid progenitors in globin gene expression, and insights into pharmacologic mechanisms of glucocorticoids and pomalidomide. Summary Immunophenotypic and molecular characterization resolves the diversity of erythroid progenitors and may ultimately lead to the ability to target these progenitors to ameliorate diseases of dyserythropoiesis.

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Section: Erythroid Progenitors As a Target For Treating Disordered Ermentioning

confidence: 99%

Characterization, regulation, and targeting of erythroid progenitors in normal and disordered human erythropoiesis

Dulmovits

Hom

Narla

et al. 2017

Current Opinion in Hematology

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“…Colonies to be used for molecular analyses were suspended in medium containing either fetal calf serum or fetal sheep serum. Coionies to be used for globin biosynthesis were placed on the bottom of microfuge tubes and processed as described (5,7).…”

Section: Methodsmentioning

confidence: 99%

“…Previous analysis of Hb F modulation in culture has relied on two methods: globin biosynthesis or labeling the culture cells with fluorescent anti-globin chain antibodies (6,7). We wished to learn whether the modulation of Hb F expression in the adult erythroid cells is controlled at the post-transcriptional or at the transcriptional level.…”

mentioning

confidence: 99%

The modulation of Hb F synthesis in adult erythroid progenitor (burst-forming unit) cultures reflects changes in gamma-globin gene transcription and chromatin structure.

Groudine

Peretz

Nakamoto

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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Fetal hemoglobin production can be reactivated in vivo in adult persons with various hemoglobinopathies and other hemopoietic disorders, and in cultures of adult erythroid progenitors. We show that the activation of Hb F in adult cells is transcriptional in nature and is accompanied by the appearance of DNase I-hypersensitive sites and undermethylation of Hpa II sites 5' to the y-globin genes. Production of Hb F in culture is strongly modulated by the environment, and the repression of Hb F synthesis by specific culture conditions has been reported. By nuclear runoff, chromatin, and methylation analyses, we show that this inhibition of Hb F production in vitro is at the level of transcription with the concomitant loss of characteristic y hypersensitive sites and methylation of Y Hpa II sites. These data indicate, first, that the organization of globin chromatin of adult cells that produce fetal hemoglobin resembles that of fetal erythroid cells and, second, that this organization switches from a fetal to an adult pattern in response to changes in the environment of the erythroid cells.

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Identification of fetal nucleated red cells in co‐cultures from fetal and adult peripheral blood: differential effects of serum on fetal and adult erythropoiesis

1999

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Direct evidence for interaction between human erythroid progenitor cells and a hemoglobin switching activity present in fetal sheep serum.

Cited by 19 publications

References 19 publications

Characterization, regulation, and targeting of erythroid progenitors in normal and disordered human erythropoiesis

Characterization, regulation, and targeting of erythroid progenitors in normal and disordered human erythropoiesis

The modulation of Hb F synthesis in adult erythroid progenitor (burst-forming unit) cultures reflects changes in gamma-globin gene transcription and chromatin structure.

Identification of fetal nucleated red cells in co‐cultures from fetal and adult peripheral blood: differential effects of serum on fetal and adult erythropoiesis

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