Research on the Function of CXCL2 During Megakaryocyte Differentiation

doi:10.19586/j.2095-2341.2022.0217

Current Biotechnology ›› 2023, Vol. 13 ›› Issue (2): 257-263.DOI: 10.19586/j.2095-2341.2022.0217

• Articles • Previous Articles Next Articles

Research on the Function of CXCL2 During Megakaryocyte Differentiation

Di WANG¹^,²(), Yanhong ZHAO¹^,², Yipeng LIANG¹^,², Haoze SONG¹^,², Lihong SHI¹^,²(), Jingyuan TONG¹^,²()

^1.State Key Laboratory of Experimental Hematology，National Clinical Research Center for Blood Diseases，Haihe Laboratory of Cell Ecosystem，Institute of Hematology & Blood Diseases Hospital，Chinese Academy of Medical Sciences & Peking Union Medical College，Tianjin 300020，China
^2.Tianjin Institutes of Health Science，Tianjin 301600，China

Received:2022-12-30 Accepted:2023-02-07 Online:2023-03-25 Published:2023-04-07
Contact: Lihong SHI,Jingyuan TONG

Abstract

Abstract:

Clinically， the conflict between supply and demand of platelet transfusion is becoming increasingly acute， and research related to platelet generation in vitro has received extensive attention globally， mainly focusing on stem cell sources， cytokines， transcription factors， and turbulent flow systems. As platelets are small fragments produced from megakaryocytes， promoting differentiation efficiency and production of megakaryocytes will optimize platelet generation in vitro. CXCL2 is a chemoattractant chemokine promoting inflammation and angiogenesis， which has been known to be associated with cardiovascular disease and colon cancer， but its function in megakaryocyte differentiation remains unclear. In this study， utilizing a model of differentiation from cord blood-derived CD34⁺ cells to megakaryocytes， CXCL2 expression was decreased by lentivirus-mediated knockdown method， and the differentiation efficiency of megakaryocytes was detected by flow cytometry. Results indicated that early stage of megakaryocyte differentiation was inhibited after CXCL2 knockdown， and this inhibitory effect persisted throughout the differentiation process. This study suggested that CXCL2 plays an important regulatory role in megakaryocyte differentiation， and this finding may exert some implications on megakaryocyte differentiation and platelet generation in vitro.

Key words: megakaryocyte differentiation, CXCL2, CD34⁺ cells

CLC Number:

Q254

Di WANG, Yanhong ZHAO, Yipeng LIANG, Haoze SONG, Lihong SHI, Jingyuan TONG. Research on the Function of CXCL2 During Megakaryocyte Differentiation[J]. Current Biotechnology, 2023, 13(2): 257-263.

Add to citation manager EndNote|Ris|BibTeX

URL: https://swjsjz.magtechjournal.com/EN/10.19586/j.2095-2341.2022.0217

https://swjsjz.magtechjournal.com/EN/Y2023/V13/I2/257

Figures/Tables 5

References 27

1	LIU C, WU D, XIA M, et al.. Characterization of cellular heterogeneity and an immune subpopulation of human megakaryocytes[J/OL]. Adv. Sci., 2021, 8(15): e2100921[2021-05-26]. .
2	NOETZLI L J, FRENCH S L, MACHLUS K R. New insights into the differentiation of megakaryocytes from hematopoietic progenitors[J]. Arterioscler Thromb. Vasc. Biol., 2019, 39(7): 1288-1300.
3	CHANG Y, BLUTEAU D, DEBILI N, et al.. From hematopoietic stem cells to platelets[J]. J. Thromb. Haemost., 2007, 5(S1): 318-327.
4	ONO-URUGA Y, IKEDA Y, MATSUBARA Y. Platelet production using adipose-derived mesenchymal stem cells: mechanistic studies and clinical application[J]. J. Thromb. Haemost., 2021, 19(2): 342-350.
5	YANG Y, LIU C, LEI X, et al.. Integrated biophysical and biochemical signals augment megakaryopoiesis and thrombopoiesis in a three-dimensional rotary culture system[J]. Stem Cells Transl. Med., 2016, 5(2): 175-185.
6	REEMS J A. A journey to produce platelets in vitro[J]. Transfusion, 2011, 51(S4): 169-176.
7	MARINI I, RIGONI F, ZLAMAL J, et al.. Blood donor-derived buffy coat to produce platelets in vitro[J]. Vox Sang., 2020, 115(1): 94-102.
8	ZLOTNIK A, YOSHIE O. The chemokine superfamily revisited[J]. Immunity, 2012, 36(5): 705-716.
9	ISRAEL F C, RICHARD M R. The many roles of chemokines and chemokine receptors in inflammation[J]. N. Engl. J. Med., 2006, 354: 610-621.
10	GEWIRTZ A M, ZHANG J, RATAJCZAK J, et al.. Chemokine regulation of human megakaryocytopoiesis[J]. Blood, 1995, 86(7): 2559-2567.
11	LU X, WANG Z, YE D, et al.. The role of CXC chemokines in cardiovascular diseases[J/OL]. Front. Pharmacol., 2022, 12: 3830[2022-05-20]. .
12	吴静,张英楠,徐长禄,等.碳酸酐酶在红细胞分化发育过程中的功能研究[J].生物技术进展,2022,12(4):582-590.
13	VISHAL S, PETROS P, LAURA G. Culture of megakaryocytes from human peripheral blood mononuclear cells[J/OL]. Bio-protocol, 2015, 5(21): e1639[2015-11-05]. .
14	YANG J G, WANG L L, MA D C. Effects of vascular endothelial growth factors and their receptors on megakaryocytes and platelets and related diseases[J]. Br. J. Haematol., 2018, 180(3): 321-334.
15	NOVERSHTERN N, SUBRAMANIAN A, LAWTON L N, et al.. Densely interconnected transcriptional circuits control cell states in human hematopoiesis[J]. Cell, 2011, 144(2): 296-309.
16	GEWIRTZ A M, CALABRETTA B, RUCINSKI B, et al.. Inhibition of human megakaryocytopoiesis in vitro by platelet factor 4 (PF4) and a synthetic COOH-terminal PF4 peptide[J]. J. Clin. Invest., 1989, 83(5): 1477-1486.
17	HAN Z C, SENSEBE L, ABGRALL J F, et al.. Platelet factor 4 inhibits human megakaryocytopoiesis in vitro[J]. Blood, 1990, 75(6): 1234-1239.
18	ESLIN D E, ZHANG C, SAMUELS K J, et al.. Transgenic mice studies demonstrate a role for platelet factor 4 in thrombosis: dissociation between anticoagulant and antithrombotic effect of heparin[J]. Blood, 2004, 104(10): 3173-3180.
19	PILLAI M M, IWATA M, AWAYA N, et al.. Monocyte-derived CXCL7 peptides in the marrow microenvironment[J]. Blood, 2006, 107(9): 3520-3526.
20	GUERRIERO R, MATTIA G, TESTA U, et al.. Stromal cell-derived factor 1 alpha increases polyploidization of megakaryocytes generated by human hematopoietic progenitor cells[J]. Blood, 2001, 97(9): 2587-2595.
21	GOODLA L, XUE X. The role of inflammatory mediators in colorectal cancer hepatic metastasis[J/OL]. Cells, 2022, 11(15): 2313[2022-07-27]. .
22	JIA S N, HAN Y B, YANG R, et al.. Chemokines in colon cancer progression[J]. Semin. Cancer Biol., 2022, 86(P3): 400-407.
23	TAKI M, ABIKO K, BABA T, et al.. Snail promotes ovarian cancer progression by recruiting myeloid-derived suppressor cells via CXCR2 ligand upregulation[J/OL]. Nat. Commun., 2018, 9(1): 1685[2018-04-27]. .
24	LENTINI G, FAMA A, BIONDO C, et al.. Neutrophils enhance their own influx to sites of bacterial infection via endosomal TLR-dependent CXCL2 production[J]. J. Immunol., 2020, 204(3): 660-670.
25	CATE H, LAMMLE B. The latest clinical advances in Thrombocytopenia[J/OL]. J. Clin. Med., 2021, 10(16):3463 [2021-08-05]. .
26	LIEBERMAN L, LIU Y, BARTY R, et al.. Platelet transfusion practice and platelet refractoriness for a cohort of pediatric oncology patients: a single-center study[J/OL]. Pediatr. Blood Cancer, 2020, 67(12): e28734[2020-09-25]. .
27	SUGIMOTO N, ETO K. Generation and manipulation of human iPSC-derived platelets[J]. Cell Mol. Life Sci., 2021, 78(7): 3385-3401.

引物名称	shRNA序列（5'→3')
Scrambled-F	5'-GTGCGTTGTTAGTACTAATCCTATTT-3'
Scrambled-R	5'-AAATAGGATTAGTACTAACAACGCAC-3'
CXCL2-sh1F	5'-GCATCGCCCATGGTTAAGAAA-3'
CXCL2-sh1R	5'-TTTCTTAACCATGGGCGATGC-3'
CXCL2-sh2F	5'-ACACTCAAGAATGGGCAGAAA-3'
CXCL2-sh2R	5'-TTTCTGCCCATTCTTGAGTGT-3'
CXCL2-sh3F	5'-GCAGATATTCTCTAGTCATTT-3'
CXCL2-sh3R	5'-AAATGACTAGAGAATATCTGC-3'
CXCL2-sh4F	5'-ATTTCTTCGTGATGACATATC-3'
CXCL2-sh4R	5'-GATATGTCATCACGAAGAAAT-3'

引物名称	shRNA序列（5'→3')
Scrambled-F	5'-GTGCGTTGTTAGTACTAATCCTATTT-3'
Scrambled-R	5'-AAATAGGATTAGTACTAACAACGCAC-3'
CXCL2-sh1F	5'-GCATCGCCCATGGTTAAGAAA-3'
CXCL2-sh1R	5'-TTTCTTAACCATGGGCGATGC-3'
CXCL2-sh2F	5'-ACACTCAAGAATGGGCAGAAA-3'
CXCL2-sh2R	5'-TTTCTGCCCATTCTTGAGTGT-3'
CXCL2-sh3F	5'-GCAGATATTCTCTAGTCATTT-3'
CXCL2-sh3R	5'-AAATGACTAGAGAATATCTGC-3'
CXCL2-sh4F	5'-ATTTCTTCGTGATGACATATC-3'
CXCL2-sh4R	5'-GATATGTCATCACGAAGAAAT-3'

Research on the Function of CXCL2 During Megakaryocyte Differentiation

RichHTML

PDF

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 5

References 27

Related Articles 0

Recommended Articles

Metrics

Comments