Molecular and epigenetic alterations in normal and malignant myelopoiesis in human leukemia 60 (HL60) promyelocytic cell line model
In vitro cell line model systems are essential in supporting the research community due to their low cost, uniform culturing conditions, homogeneous biological resources, and easy experimental design to study the cause and effect of a gene or a molecule. Human leukemia 60 (HL60) is an in-vitro hemat...
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| Format: | Article |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1060537/full |
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| author | Jhinuk Basu Jhinuk Basu Swati Madhulika Swati Madhulika Krushna Chandra Murmu Krushna Chandra Murmu Smrutishree Mohanty Smrutishree Mohanty Priyanka Samal Asima Das Soumendu Mahapatra Soumendu Mahapatra Subha Saha Indranil Sinha Punit Prasad |
| author_facet | Jhinuk Basu Jhinuk Basu Swati Madhulika Swati Madhulika Krushna Chandra Murmu Krushna Chandra Murmu Smrutishree Mohanty Smrutishree Mohanty Priyanka Samal Asima Das Soumendu Mahapatra Soumendu Mahapatra Subha Saha Indranil Sinha Punit Prasad |
| author_sort | Jhinuk Basu |
| collection | DOAJ |
| description | In vitro cell line model systems are essential in supporting the research community due to their low cost, uniform culturing conditions, homogeneous biological resources, and easy experimental design to study the cause and effect of a gene or a molecule. Human leukemia 60 (HL60) is an in-vitro hematopoietic model system that has been used for decades to study normal myeloid differentiation and leukemia biology. Here, we show that IMDM supplemented with 20% FBS is an optimal culturing condition and induces effective myeloid differentiation compared with RPMI supplemented with 10% FBS when HL60 is induced with 1α,25-dihydroxyvitamin D3 (Vit D3) and all-trans retinoic acid (ATRA). The chromatin organization is compacted, and the repressive epigenetic mark H3K27me3 is enhanced upon HL60-mediated terminal differentiation. Differential gene expression analysis obtained from RNA sequencing in HL60 cells during myeloid differentiation showed the induction of pathways involved in epigenetic regulation, myeloid differentiation, and immune regulation. Using high-throughput transcriptomic data (GSE74246), we show the similarities (genes that did not satisfy |log2FC|>1 and FDR<0.05) and differences (FDR <0.05 and |log2FC|>1) between granulocyte-monocyte progenitor vs HL60 cells, Vit D3 induced monocytes (vMono) in HL60 cells vs primary monocytes (pMono), and HL60 cells vs leukemic blasts at the transcriptomic level. We found striking similarities in biological pathways between these comparisons, suggesting that the HL60 model system can be effectively used for studying myeloid differentiation and leukemic aberrations. The differences obtained could be attributed to the fact that the cellular programs of the leukemic cell line and primary cells are different. We validated several gene expression patterns for different comparisons with CD34+ cells derived from cord blood for myeloid differentiation and AML patients. In addition to the current knowledge, our study further reveals the significance of using HL60 cells as in vitro model system under optimal conditions to understand its potential as normal myeloid differentiation model as well as leukemic model at the molecular level. |
| first_indexed | 2024-04-10T18:07:18Z |
| format | Article |
| id | doaj.art-8e5eb73aef0f4cc28ab480f2fc3aebcf |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-10T18:07:18Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-8e5eb73aef0f4cc28ab480f2fc3aebcf2023-02-02T12:48:39ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-02-011110.3389/fcell.2023.10605371060537Molecular and epigenetic alterations in normal and malignant myelopoiesis in human leukemia 60 (HL60) promyelocytic cell line modelJhinuk Basu0Jhinuk Basu1Swati Madhulika2Swati Madhulika3Krushna Chandra Murmu4Krushna Chandra Murmu5Smrutishree Mohanty6Smrutishree Mohanty7Priyanka Samal8Asima Das9Soumendu Mahapatra10Soumendu Mahapatra11Subha Saha12Indranil Sinha13Punit Prasad14Chromatin and Epigenetics Unit, Institute of Life Sciences, Bhubaneswar, IndiaRCB, Regional Centre for Biotechnology, Faridabad, IndiaChromatin and Epigenetics Unit, Institute of Life Sciences, Bhubaneswar, IndiaRCB, Regional Centre for Biotechnology, Faridabad, IndiaChromatin and Epigenetics Unit, Institute of Life Sciences, Bhubaneswar, IndiaRCB, Regional Centre for Biotechnology, Faridabad, IndiaChromatin and Epigenetics Unit, Institute of Life Sciences, Bhubaneswar, IndiaRCB, Regional Centre for Biotechnology, Faridabad, IndiaIMS and SUM Hospital, Siksha ‘O' Anusandhan University, Bhubaneswar, IndiaDepartment of Obstetrics and Gynecology, KIMS, Bhubaneswar, IndiaChromatin and Epigenetics Unit, Institute of Life Sciences, Bhubaneswar, IndiaKalinga Institute of Industrial Technology (KIIT), School of Biotechnology, Bhubaneswar, IndiaChromatin and Epigenetics Unit, Institute of Life Sciences, Bhubaneswar, IndiaChildhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Solna, SwedenChromatin and Epigenetics Unit, Institute of Life Sciences, Bhubaneswar, IndiaIn vitro cell line model systems are essential in supporting the research community due to their low cost, uniform culturing conditions, homogeneous biological resources, and easy experimental design to study the cause and effect of a gene or a molecule. Human leukemia 60 (HL60) is an in-vitro hematopoietic model system that has been used for decades to study normal myeloid differentiation and leukemia biology. Here, we show that IMDM supplemented with 20% FBS is an optimal culturing condition and induces effective myeloid differentiation compared with RPMI supplemented with 10% FBS when HL60 is induced with 1α,25-dihydroxyvitamin D3 (Vit D3) and all-trans retinoic acid (ATRA). The chromatin organization is compacted, and the repressive epigenetic mark H3K27me3 is enhanced upon HL60-mediated terminal differentiation. Differential gene expression analysis obtained from RNA sequencing in HL60 cells during myeloid differentiation showed the induction of pathways involved in epigenetic regulation, myeloid differentiation, and immune regulation. Using high-throughput transcriptomic data (GSE74246), we show the similarities (genes that did not satisfy |log2FC|>1 and FDR<0.05) and differences (FDR <0.05 and |log2FC|>1) between granulocyte-monocyte progenitor vs HL60 cells, Vit D3 induced monocytes (vMono) in HL60 cells vs primary monocytes (pMono), and HL60 cells vs leukemic blasts at the transcriptomic level. We found striking similarities in biological pathways between these comparisons, suggesting that the HL60 model system can be effectively used for studying myeloid differentiation and leukemic aberrations. The differences obtained could be attributed to the fact that the cellular programs of the leukemic cell line and primary cells are different. We validated several gene expression patterns for different comparisons with CD34+ cells derived from cord blood for myeloid differentiation and AML patients. In addition to the current knowledge, our study further reveals the significance of using HL60 cells as in vitro model system under optimal conditions to understand its potential as normal myeloid differentiation model as well as leukemic model at the molecular level.https://www.frontiersin.org/articles/10.3389/fcell.2023.1060537/fullHL60chromatintranscriptomenormal myeloid differentiationacute myeloid leukemia (AML) |
| spellingShingle | Jhinuk Basu Jhinuk Basu Swati Madhulika Swati Madhulika Krushna Chandra Murmu Krushna Chandra Murmu Smrutishree Mohanty Smrutishree Mohanty Priyanka Samal Asima Das Soumendu Mahapatra Soumendu Mahapatra Subha Saha Indranil Sinha Punit Prasad Molecular and epigenetic alterations in normal and malignant myelopoiesis in human leukemia 60 (HL60) promyelocytic cell line model Frontiers in Cell and Developmental Biology HL60 chromatin transcriptome normal myeloid differentiation acute myeloid leukemia (AML) |
| title | Molecular and epigenetic alterations in normal and malignant myelopoiesis in human leukemia 60 (HL60) promyelocytic cell line model |
| title_full | Molecular and epigenetic alterations in normal and malignant myelopoiesis in human leukemia 60 (HL60) promyelocytic cell line model |
| title_fullStr | Molecular and epigenetic alterations in normal and malignant myelopoiesis in human leukemia 60 (HL60) promyelocytic cell line model |
| title_full_unstemmed | Molecular and epigenetic alterations in normal and malignant myelopoiesis in human leukemia 60 (HL60) promyelocytic cell line model |
| title_short | Molecular and epigenetic alterations in normal and malignant myelopoiesis in human leukemia 60 (HL60) promyelocytic cell line model |
| title_sort | molecular and epigenetic alterations in normal and malignant myelopoiesis in human leukemia 60 hl60 promyelocytic cell line model |
| topic | HL60 chromatin transcriptome normal myeloid differentiation acute myeloid leukemia (AML) |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1060537/full |
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