The Pleiotropic Effects of GATA1 and KLF1 in Physiological Erythropoiesis and in Dyserythropoietic Disorders

Abstract

In the last few years, the advent of new technological approaches has led to a better knowledge of the ontogeny of erythropoiesis during development and of the journey leading from hematopoietic stem cells (HSCs) to mature red blood cells (RBCs). Our view of a well-defined hierarchical model of hematopoiesis with a near-homogeneous HSC population residing at the apex has been progressively challenged in favor of a landscape where HSCs themselves are highly heterogeneous and lineages separate earlier than previously thought. The coordination of these events is orchestrated by transcription factors (TFs) that work in a combinatorial manner to activate and/or repress their target genes. The development of next generation sequencing (NGS) has facilitated the identification of pathological mutations involving TFs underlying hematological defects. The examples of GATA1 and KLF1 presented in this review suggest that in the next few years the number of TF mutations associated with dyserythropoietic disorders will further increase.

Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria

“…This study provides evidence that vaccination, using a non-infectious vaccine consisting of erythrocyte ghosts isolated from P. chabaudi-infected erythrocytes, accelerates expression of erythroid genes in the liver induced by blood-stage malaria of P. chabaudi. Indeed, these genes encompass Slc4a1 and Gypa encoding band 3 and Glycophorin A, major integral membrane proteins of red blood cells; Rhd, Kel and Rhag coding for blood group antigens and Rh-associated antigen glycoprotein exposed on the outer membrane surface of red blood cells; Ermap and Cldn1 encoding presumably proteins associated with the outer surface of erythroblasts [25]; Add2 and Ank1 coding for proteins linking integral membrane proteins with peripheral skeletal proteins located on the inner surface of erythroid cells, as e.g., Epb4.2, Epb4.9, Spta, and Sptb [45,46]; Acyp1 and Ahsp encoding proteins within erythroid cells; and even Gata1, Gfi1b, Tal1 and Klf1 coding for transcription factors critically involved in erythropoiesis [47][48][49]. Expression of these genes takes an accelerated time-course in surviving vaccinated mice, evidenced as it is significantly higher at early patency on day 4 p.i.…”

“…Gene expression levels The genes Gata1, Gfi1b, Klf1, and Tal1 encode transcription factors which are known to be critically involved in erythropoiesis [47][48][49]. These genes also reach high expressions between approximately 80 and 110 above the normalization level towards the end of the crisis phase (Fig.…”

Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria

“…This study provides evidence that vaccination, using a non-infectious vaccine consisting of erythrocyte ghosts isolated from P. chabaudi-infected erythrocytes, accelerates expression of erythroid genes in the liver induced by blood-stage malaria of P. chabaudi. Indeed, these genes encompass Slc4a1 and Gypa encoding band 3 and glycophorin A, major integral membrane proteins of red blood cells; Rhd, Kel and Rhag coding for blood group antigens and Rh-associated antigen glycoprotein exposed on the outer membrane surface of red blood cells; Ermap and Cldn1 encoding presumably proteins associated with the outer surface of erythroblasts [25]; Add2 and Ank1 coding for proteins linking integral membrane proteins with peripheral skeletal proteins located on the inner surface of erythroid cells, as e.g., Epb4.2, Epb4.9, Spta, and Sptb [45,46]; Acyp1 and Ahsp encoding proteins within erythroid cells; and even Gata1, Gfi1b, Tal1 and Klf1 coding for transcription factors critically involved in erythropoiesis [47][48][49]. Expression of these genes takes an accelerated timecourse in surviving vaccinated mice, evidenced as it is significantly higher at early patency on day 4 p.i.…”

“…The genes Gata1, Gfi1b, Klf1, and Tal1 encode transcription factors which are known to be critically involved in erythropoiesis [47][48][49]. These genes also reach high expressions between approximately 80 and 110 above the normalization level towards the end of the crisis phase (Fig.…”

Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria

“…This study provides evidence that vaccination, using a non-infectious vaccine consisting of erythrocyte ghosts isolated from P. chabaudi-infected erythrocytes, accelerates expression of erythroid genes in the liver induced by blood-stage malaria of P. chabaudi. Indeed, these genes encompass Slc4a1 and Gypa encoding band 3 and glycophorin A, major integral membrane proteins of red blood cells; Rhd, Kel and Rhag coding for blood group antigens and Rh-associated antigen glycoprotein exposed on the outer membrane surface of red blood cells; Ermap and Cldn1 encoding presumably proteins associated with the outer surface of erythroblasts [25]; Add2 and Ank1 coding for proteins linking integral membrane proteins with peripheral skeletal proteins located on the inner surface of erythroid cells, as e.g., Epb4.2, Epb4.9, Spta, and Sptb [45,46]; Acyp1 and Ahsp encoding proteins within erythroid cells; and even Gata1, Gfi1b, Tal1 and Klf1 coding for transcription factors critically involved in erythropoiesis [47][48][49]. Expression of these genes takes an accelerated timecourse in surviving vaccinated mice, evidenced as it is significantly higher at early patency on day 4 p.i.…”