Induction of adult levels of  -globin in human erythroid cells that intrinsically express embryonic or fetal globin by transduction with KLF1 and BCL11A-XL

Trakarnsanga, Kongtana; Wilson, Marieangela C.; Lau, Winnie; Singleton, Belinda K.; Parsons, Stephen; Sakuntanaga, Punthita; Kurita, Ryo; Nakamura, Yukio; Anstee, David J.; Frayne, Jan

doi:10.3324/haematol.2014.110155

Cited by 51 publications

(54 citation statements)

References 44 publications

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“…This would identify key regulators of hemoglobin expression in iEP as well as improve the potential of these cells for therapeutic applications, as highlighted by Trakarnsanga et al (2014). We evaluated the transcription factors Sox6, Bcl11a, Klf1, and Myb, all previously identified to directly or indirectly downregulate the expression of embryonic and fetal globin genes (Sankaran et al, 2009Yi et al, 2006;Zhou et al, 2010).…”

Section: Induction Of Adult Globin Expression By Klf1 and Mybmentioning

confidence: 99%

Defining the minimal factors required for erythropoiesis through direct lineage conversion

Capellera-Garcia

Pulecio

Dhulipala

et al. 2016

Experimental Hematology

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SUMMARYErythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of well characterized genes. However, the minimal set of factors necessary for instructing red blood cell (RBC) development remains undefined. We employed a screen for transcription factors allowing direct lineage reprograming from fibroblasts to induced erythroid progenitors/precursors (iEPs). We show that Gata1, Tal1, Lmo2, and c-Myc (GTLM) can rapidly convert murine and human fibroblasts directly to iEPs. The transcriptional signature of murine iEPs resembled mainly that of primitive erythroid progenitors in the yolk sac, whereas addition of Klf1 or Myb to the GTLM cocktail resulted in iEPs with a more adult-type globin expression pattern. Our results demonstrate that direct lineage conversion is a suitable platform for defining and studying the core factors inducing the different waves of erythroid development.

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Section: Induction Of Adult Globin Expression By Klf1 and Mybmentioning

confidence: 99%

Defining the minimal factors required for erythropoiesis through direct lineage conversion

Capellera-Garcia

Pulecio

Dhulipala

et al. 2016

Experimental Hematology

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“…Membranes were blocked with 10% milk powder for 1 h, followed by incubation with primary antibodies overnight at 4°C. Primary antibodies used were aquaporin I (CHIP28) and glycophorin A (CVDP) 1:1000 dilution, ankyrin 1 (BRIC274) 1:100 dilution, and band 3 (BRIC170) 1 (15,16).…”

Section: Isolation Of Adult and Cord Blood Rbcs And Cd34mentioning

confidence: 99%

“…Globin expression was analyzed using primers to ␤-globin 5Ј CTTTAGTGATG-GCCTGGCTC and 5Ј GGCAGAATCCAGATGCTCAA, and ␥-globin 5Ј GGGCAAGGTGAATGTGGAAGAT and 5Ј GGGTCCATGGGTA-GACAACCA as described previously (15).…”

Section: Isolation Of Adult and Cord Blood Rbcs And Cd34mentioning

confidence: 99%

Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation

Wilson

Trakarnsanga

Heesom

et al. 2016

Molecular & Cellular Proteomics

105

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Cord blood stem cells are an attractive starting source for the production of red blood cells in vitro for therapy because of additional expansion potential compared with adult peripheral blood progenitors and cord blood banks usually being more representative of national populations than blood donors. Consequently, it is important to establish how similar cord RBCs are to adult cells. In this study, we used multiplex tandem mass tag labeling combined with nano-LC-MS/MS to compare the proteome of adult and cord RBCs and reticulocytes. 2838 unique proteins were identified, providing the most comprehensive compendium of RBC proteins to date. Using stringent criteria, 1674 proteins were quantified, and only a small number differed in amount between adult and cord RBC. We focused on proteins critical for RBC function. Of these, only the expected differences in globin subunits, along with higher levels of carbonic anhydrase 1 and 2 and aquaporin-1 in adult RBCs would be expected to have a phenotypic effect since they are associated with the differences in gaseous exchange between adults and neonates. Since the RBC and reticulocyte samples used were autologous, we catalogue the change in proteome following reticulocyte maturation. The majority of proteins (>60% of the 1671 quantified) reduced in abundance between 2-and 100-fold following maturation. However, ϳ5% were at a higher level in RBCs, localized almost exclusively to cell membranes, in keeping with the known clearance of intracellular recycling pools during reticulocyte maturation. Overall, these data suggest that, with respect to the proteome, there is no barrier to the use of cord progenitors for the in vitro generation of RBCs for transfusion to adults other than the expression of fetal, not adult, hemoglobin. Molecular & Cellular Proteomics

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“…In this issue of Haematologica, Trakarnasanga et al 1 demonstrate that forced expression of KLF1 and BCL11A induces switching to adult hemoglobin expression in erythroid cells derived from cord blood and hiPS cells.…”

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confidence: 99%

Flicking the switch: adult hemoglobin expression in erythroid cells derived from cord blood and human induced pluripotent stem cells

Cantù

Philipsen

2014

Haematologica

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Induction of adult levels of -globin in human erythroid cells that intrinsically express embryonic or fetal globin by transduction with KLF1 and BCL11A-XL

Cited by 51 publications

References 44 publications

Defining the minimal factors required for erythropoiesis through direct lineage conversion

Defining the minimal factors required for erythropoiesis through direct lineage conversion

Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation

Flicking the switch: adult hemoglobin expression in erythroid cells derived from cord blood and human induced pluripotent stem cells

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