Improving hematopoietic differentiation from human induced pluripotent stem cells by the modulation of Hippo signaling with a diarylheptanoid derivative.
Diarylheptanoid
Hippo signaling pathway
Human induced pluripotent stem cells
Primitive hematopoietic stem and progenitor cells
Journal
Stem cell research & therapy
ISSN: 1757-6512
Titre abrégé: Stem Cell Res Ther
Pays: England
ID NLM: 101527581
Informations de publication
Date de publication:
03 Mar 2024
03 Mar 2024
Historique:
received:
04
07
2023
accepted:
27
02
2024
medline:
4
3
2024
pubmed:
4
3
2024
entrez:
3
3
2024
Statut:
epublish
Résumé
The diarylheptanoid ASPP 049 has improved the quality of adult hematopoietic stem cell (HSC) expansion ex vivo through long-term reconstitution in animal models. However, its effect on hematopoietic regeneration from human induced pluripotent stem cells (hiPSCs) is unknown. We utilized a defined cocktail of cytokines without serum or feeder followed by the supplementation of ASPP 049 to produce hematopoietic stem/progenitor cells (HSPCs). Flow cytometry and trypan blue exclusion analysis were used to identify nonadherent and adherent cells. Nonadherent cells were harvested to investigate the effect of ASPP 049 on multipotency using LTC-IC and CFU assays. Subsequently, the mechanism of action was explored through transcriptomic profiles, which were validated by qRT-PCR, immunoblotting, and immunofluorescence analysis. The supplementation of ASPP 049 increased the number of phenotypically defined primitive HSPCs (CD34 These findings suggest that ASPP 049 can improve HSC-generating protocols with proliferative potentials, self-renewal ability, unbiased differentiation, and a definable mechanism of action for the clinical perspective of hematopoietic regenerative medicine.
Sections du résumé
BACKGROUND
BACKGROUND
The diarylheptanoid ASPP 049 has improved the quality of adult hematopoietic stem cell (HSC) expansion ex vivo through long-term reconstitution in animal models. However, its effect on hematopoietic regeneration from human induced pluripotent stem cells (hiPSCs) is unknown.
METHOD
METHODS
We utilized a defined cocktail of cytokines without serum or feeder followed by the supplementation of ASPP 049 to produce hematopoietic stem/progenitor cells (HSPCs). Flow cytometry and trypan blue exclusion analysis were used to identify nonadherent and adherent cells. Nonadherent cells were harvested to investigate the effect of ASPP 049 on multipotency using LTC-IC and CFU assays. Subsequently, the mechanism of action was explored through transcriptomic profiles, which were validated by qRT-PCR, immunoblotting, and immunofluorescence analysis.
RESULT
RESULTS
The supplementation of ASPP 049 increased the number of phenotypically defined primitive HSPCs (CD34
CONCLUSION
CONCLUSIONS
These findings suggest that ASPP 049 can improve HSC-generating protocols with proliferative potentials, self-renewal ability, unbiased differentiation, and a definable mechanism of action for the clinical perspective of hematopoietic regenerative medicine.
Identifiants
pubmed: 38433217
doi: 10.1186/s13287-024-03686-4
pii: 10.1186/s13287-024-03686-4
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
60Subventions
Organisme : Mahidol University
ID : MU's Strategic Research Fund: fiscal year 2023
Organisme : National Research Council of Thailand
ID : N41A660154
Organisme : Ministry of Science and Technology of Thailand
ID : the Science Achievement Scholarship of Thailand
Organisme : Faculty of Science, Mahidol University
ID : the Central Instrument Facility (CIF)
Informations de copyright
© 2024. The Author(s).
Références
Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861–72.
pubmed: 18035408
doi: 10.1016/j.cell.2007.11.019
Rowe RG, Daley GQ. Induced pluripotent stem cells in disease modelling and drug discovery. Nat Rev Genet. 2019;20(7):377–88.
pubmed: 30737492
pmcid: 6584039
doi: 10.1038/s41576-019-0100-z
Hansen M, von Lindern M, van den Akker E, Varga E. Human-induced pluripotent stem cell-derived blood products: state of the art and future directions. FEBS Lett. 2019;593(23):3288–303.
pubmed: 31520530
doi: 10.1002/1873-3468.13599
Vo LT, Daley GQ. De novo generation of HSCs from somatic and pluripotent stem cell sources. Blood. 2015;125(17):2641–8.
pubmed: 25762177
pmcid: 4408289
doi: 10.1182/blood-2014-10-570234
Sugimura R, Jha DK, Han A, Soria-Valles C, da Rocha EL, Lu YF, et al. Haematopoietic stem and progenitor cells from human pluripotent stem cells. Nature. 2017;545(7655):432–8.
pubmed: 28514439
pmcid: 5872146
doi: 10.1038/nature22370
Doulatov S, Vo LT, Chou SS, Kim PG, Arora N, Li H, et al. Induction of multipotential hematopoietic progenitors from human pluripotent stem cells via respecification of lineage-restricted precursors. Cell Stem Cell. 2013;13(4):459–70.
pubmed: 24094326
doi: 10.1016/j.stem.2013.09.002
Gori JL, Butler JM, Chan YY, Chandrasekaran D, Poulos MG, Ginsberg M, et al. Vascular niche promotes hematopoietic multipotent progenitor formation from pluripotent stem cells. J Clin Invest. 2015;125(3):1243–54.
pubmed: 25664855
pmcid: 4362238
doi: 10.1172/JCI79328
Kennedy M, Awong G, Sturgeon CM, Ditadi A, LaMotte-Mohs R, Zuniga-Pflucker JC, et al. T lymphocyte potential marks the emergence of definitive hematopoietic progenitors in human pluripotent stem cell differentiation cultures. Cell Rep. 2012;2(6):1722–35.
pubmed: 23219550
doi: 10.1016/j.celrep.2012.11.003
Sturgeon CM, Ditadi A, Awong G, Kennedy M, Keller G. Wnt signaling controls the specification of definitive and primitive hematopoiesis from human pluripotent stem cells. Nat Biotechnol. 2014;32(6):554–61.
pubmed: 24837661
pmcid: 4152856
doi: 10.1038/nbt.2915
Choi KD, Vodyanik MA, Togarrati PP, Suknuntha K, Kumar A, Samarjeet F, et al. Identification of the hemogenic endothelial progenitor and its direct precursor in human pluripotent stem cell differentiation cultures. Cell Rep. 2012;2(3):553–67.
pubmed: 22981233
pmcid: 3462245
doi: 10.1016/j.celrep.2012.08.002
Lacaud G, Kouskoff V. Hemangioblast, hemogenic endothelium, and primitive versus definitive hematopoiesis. Exp Hematol. 2017;49:19–24.
pubmed: 28043822
doi: 10.1016/j.exphem.2016.12.009
Slukvin I. Hematopoietic specification from human pluripotent stem cells current advances and challenges toward de novo generation of hematopoietic stem cells. Blood. 2013;122:25.
doi: 10.1182/blood-2013-07-474825
Canu G, Ruhrberg C. First blood: the endothelial origins of hematopoietic progenitors. Angiogenesis. 2021;24(2):199–211.
pubmed: 33783643
pmcid: 8205888
doi: 10.1007/s10456-021-09783-9
Lange L, Morgan M, Schambach A. The hemogenic endothelium: a critical source for the generation of PSC-derived hematopoietic stem and progenitor cells. Cell Mol Life Sci. 2021;78(9):4143–60.
pubmed: 33559689
pmcid: 8164610
doi: 10.1007/s00018-021-03777-y
Demirci S, Leonard A, Tisdale JF. Hematopoietic stem cells from pluripotent stem cells: clinical potential, challenges, and future perspectives. Stem Cells Transl Med. 2020;9(12):1549–57.
pubmed: 32725882
pmcid: 7695636
doi: 10.1002/sctm.20-0247
Shen J, Xu Y, Zhang S, Lyu S, Huo Y, Zhu Y, et al. Single-cell transcriptome of early hematopoiesis guides arterial endothelial-enhanced functional T cell generation from human PSCs. Sci Adv. 2021;7(36):eabi9787.
pubmed: 34516916
pmcid: 8442917
doi: 10.1126/sciadv.abi9787
Grigoriadis AE, Kennedy M, Bozec A, Brunton F, Stenbeck G, Park IH, et al. Directed differentiation of hematopoietic precursors and functional osteoclasts from human ES and iPS cells. Blood. 2010;115(14):2769–76.
pubmed: 20065292
pmcid: 2854424
doi: 10.1182/blood-2009-07-234690
Galat Y, Dambaeva S, Elcheva I, Khanolkar A, Beaman K, Iannaccone PM, et al. Cytokine-free directed differentiation of human pluripotent stem cells efficiently produces hemogenic endothelium with lymphoid potential. Stem Cell Res Ther. 2017;8(1):67.
pubmed: 28302184
pmcid: 5356295
doi: 10.1186/s13287-017-0519-0
Tan YT, Ye L, Xie F, Beyer AI, Muench MO, Wang J, et al. Respecifying human iPSC-derived blood cells into highly engraftable hematopoietic stem and progenitor cells with a single factor. Proc Natl Acad Sci USA. 2018;115(9):2180–5.
pubmed: 29386396
pmcid: 5834708
doi: 10.1073/pnas.1718446115
Li X, Xia C, Wang T, Liu L, Zhao Q, Yang D, et al. Pyrimidoindole derivative UM171 enhances derivation of hematopoietic progenitor cells from human pluripotent stem cells. Stem Cell Res. 2017;21:32–9.
pubmed: 28368243
doi: 10.1016/j.scr.2017.03.014
Galat Y, Elcheva I, Dambaeva S, Katukurundage D, Beaman K, Iannaccone PM, et al. Application of small molecule CHIR99021 leads to the loss of hemangioblast progenitor and increased hematopoiesis of human pluripotent stem cells. Exp Hematol. 2018;65(38–48): e1.
Kim K, Abdal Dayem A, Gil M, Yang GM, Lee SB, Kwon OH, et al. 3,2’-Dihydroxyflavone improves the proliferation and survival of human pluripotent stem cells and their differentiation into hematopoietic progenitor cells. J Clin Med. 2020;9(3):669.
pubmed: 32131506
pmcid: 7141312
doi: 10.3390/jcm9030669
Smith BW, Rozelle SS, Leung A, Ubellacker J, Parks A, Nah SK, et al. The aryl hydrocarbon receptor directs hematopoietic progenitor cell expansion and differentiation. Blood. 2013;122(3):376–85.
pubmed: 23723449
pmcid: 3716202
doi: 10.1182/blood-2012-11-466722
Angelos MG, Kaufman DS. Advances in the role of the aryl hydrocarbon receptor to regulate early hematopoietic development. Curr Opin Hematol. 2018;25(4):273–8.
pubmed: 29697485
doi: 10.1097/MOH.0000000000000432
Mesquitta WT, Wandsnider M, Kang H, Thomson J, Moskvin O, Suknuntha K, et al. UM171 expands distinct types of myeloid and NK progenitors from human pluripotent stem cells. Sci Rep. 2019;9(1):6622.
pubmed: 31036928
pmcid: 6488662
doi: 10.1038/s41598-019-43054-4
Shim SH, Tufa D, Woods R, George TD, Shank T, Yingst A, et al. SAHA enhances differentiation of CD34
pubmed: 35349707
pmcid: 9154343
doi: 10.1093/stcltm/szac012
Suksamrarn A, Ponglikitmongkol M, Wongkrajang K, Chindaduang A, Kittidanairak S, Jankam A, et al. Diarylheptanoids, new phytoestrogens from the rhizomes of Curcuma comosa: isolation, chemical modification and estrogenic activity evaluation. Bioorg Med Chem. 2008;16(14):6891–902.
pubmed: 18554915
doi: 10.1016/j.bmc.2008.05.051
Winuthayanon W, Piyachaturawat P, Suksamrarn A, Ponglikitmongkol M, Arao Y, Hewitt SC, et al. Diarylheptanoid phytoestrogens isolated from the medicinal plant Curcuma comosa: biologic actions in vitro and in vivo indicate estrogen receptor-dependent mechanisms. Environ Health Perspect. 2009;117(7):1155–61.
pubmed: 19654927
pmcid: 2717144
doi: 10.1289/ehp.0900613
Tanhuad N, Thongsa-Ad U, Sutjarit N, Yoosabai P, Panvongsa W, Wongniam S, et al. Ex vivo expansion and functional activity preservation of adult hematopoietic stem cells by a diarylheptanoid from Curcuma comosa. Biomed Pharmacother. 2021;143: 112102.
pubmed: 34474347
doi: 10.1016/j.biopha.2021.112102
Bhukhai K, Fouquet G, Rittavee Y, Tanhuad N, Lakmuang C, Borwornpinyo S, et al. Enhancing erythropoiesis by a phytoestrogen diarylheptanoid from Curcuma comosa. Biomedicines. 2022;10(6):1427.
pubmed: 35740448
pmcid: 9219836
doi: 10.3390/biomedicines10061427
Tangprasittipap A, Jittorntrum B, Wongkummool W, Kitiyanant N, Tubsuwan A. Generation of induced pluripotent stem cells from peripheral blood CD34
pubmed: 28395748
doi: 10.1016/j.scr.2017.02.013
Daniel MG, Sachs D, Bernitz JM, Fstkchyan Y, Rapp K, Satija N, et al. Induction of human hemogenesis in adult fibroblasts by defined factors and hematopoietic coculture. FEBS Lett. 2019;593(23):3266–87.
pubmed: 31557312
pmcid: 6901732
doi: 10.1002/1873-3468.13621
Ponchio L, Duma L, Oliviero B, Gibelli N, Pedrazzoli P, Cuna GR. Mitomycin C as an alternative to irradiation to inhibit the feeder layer growth in long-term culture assays. Cytotherapy. 2000;2(4):281–6.
pubmed: 12042037
doi: 10.1080/146532400539215
Lange L, Hoffmann D, Schwarzer A, Ha TC, Philipp F, Lenz D, et al. Inducible forward programming of human pluripotent stem cells to hemato-endothelial progenitor cells with hematopoietic progenitor potential. Stem Cell Rep. 2020;15(1):274.
doi: 10.1016/j.stemcr.2020.05.019
Ronn RE, Guibentif C, Saxena S, Woods NB. Reactive oxygen species impair the function of CD90(
pubmed: 27641910
doi: 10.1002/stem.2503
Sutherland HJ, Lansdorp PM, Henkelman DH, Eaves AC, Eaves CJ. Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrow stromal layers. Proc Natl Acad Sci USA. 1990;87(9):3584–8.
pubmed: 2333304
pmcid: 53946
doi: 10.1073/pnas.87.9.3584
Moore KA, Ema H, Lemischka IR. In vitro maintenance of highly purified, transplantable hematopoietic stem cells. Blood. 1997;89(12):4337–47.
pubmed: 9192756
doi: 10.1182/blood.V89.12.4337
Trakarnsanga K, Ferguson D, Daniels DE, Griffiths RE, Wilson MC, Mordue KE, et al. Vimentin expression is retained in erythroid cells differentiated from human iPSC and ESC and indicates dysregulation in these cells early in differentiation. Stem Cell Res Ther. 2019;10(1):130.
pubmed: 31036072
pmcid: 6489253
doi: 10.1186/s13287-019-1231-z
Tubsuwan A, Abed S, Deichmann A, Kardel MD, Bartholoma C, Cheung A, et al. Parallel assessment of globin lentiviral transfer in induced pluripotent stem cells and adult hematopoietic stem cells derived from the same transplanted beta-thalassemia patient. Stem Cells. 2013;31(9):1785–94.
pubmed: 23712774
doi: 10.1002/stem.1436
Mo JS, Park HW, Guan KL. The Hippo signaling pathway in stem cell biology and cancer. EMBO Rep. 2014;15(6):642–56.
pubmed: 24825474
pmcid: 4197875
doi: 10.15252/embr.201438638
Bucar S, Branco ADM, Mata MF, Milhano JC, Caramalho I, Cabral JMS, et al. Influence of the mesenchymal stromal cell source on the hematopoietic supportive capacity of umbilical cord blood-derived CD34(
pubmed: 34256848
pmcid: 8278708
doi: 10.1186/s13287-021-02474-8
McGrath Kathleen E, Frame Jenna M, Fegan Katherine H, Bowen James R, Conway Simon J, Catherman Seana C, et al. Distinct sources of hematopoietic progenitors emerge before HSCs and provide functional blood cells in the mammalian embryo. Cell Rep. 2015;11(12):1892–904.
pubmed: 26095363
pmcid: 4490098
doi: 10.1016/j.celrep.2015.05.036
Laurenti E, Gottgens B. From haematopoietic stem cells to complex differentiation landscapes. Nature. 2018;553(7689):418–26.
pubmed: 29364285
pmcid: 6555401
doi: 10.1038/nature25022
Niwa A, Heike T, Umeda K, Oshima K, Kato I, Sakai H, et al. A novel serum-free monolayer culture for orderly hematopoietic differentiation of human pluripotent cells via mesodermal progenitors. PLoS ONE. 2011;6(7): e22261.
pubmed: 21818303
pmcid: 3144871
doi: 10.1371/journal.pone.0022261
Tursky ML, Loi TH, Artuz CM, Alateeq S, Wolvetang EJ, Tao H, et al. Direct comparison of four hematopoietic differentiation methods from human induced pluripotent stem cells. Stem Cell Reports. 2020;15(3):735–48.
pubmed: 32763163
pmcid: 7486192
doi: 10.1016/j.stemcr.2020.07.009
Hansen M, Varga E, Aarts C, Wust T, Kuijpers T, von Lindern M, et al. Efficient production of erythroid, megakaryocytic and myeloid cells, using single cell-derived iPSC colony differentiation. Stem Cell Res. 2018;29:232–44.
pubmed: 29751281
doi: 10.1016/j.scr.2018.04.016
Salvagiotto G, Burton S, Daigh CA, Rajesh D, Slukvin II, Seay NJ. A defined, feeder-free, serum-free system to generate in vitro hematopoietic progenitors and differentiated blood cells from hESCs and hiPSCs. PLoS ONE. 2011;6(3): e17829.
pubmed: 21445267
pmcid: 3060827
doi: 10.1371/journal.pone.0017829
Ruiz JP, Chen G, Haro Mora JJ, Keyvanfar K, Liu C, Zou J, et al. Robust generation of erythroid and multilineage hematopoietic progenitors from human iPSCs using a scalable monolayer culture system. Stem Cell Res. 2019;41: 101600.
pubmed: 31710911
pmcid: 6953424
doi: 10.1016/j.scr.2019.101600
Tomellini E, Fares I, Lehnertz B, Chagraoui J, Mayotte N, MacRae T, et al. Integrin-alpha3 Is a functional marker of ex vivo expanded human long-term hematopoietic stem cells. Cell Rep. 2019;28(4):1063–73.
pubmed: 31340144
doi: 10.1016/j.celrep.2019.06.084
Bhukhai K, Suksen K, Bhummaphan N, Janjorn K, Thongon N, Tantikanlayaporn D, et al. A phytoestrogen diarylheptanoid mediates estrogen receptor/Akt/glycogen synthase kinase 3beta protein-dependent activation of the Wnt/beta-catenin signaling pathway. J Biol Chem. 2012;287(43):36168–78.
pubmed: 22936801
pmcid: 3476284
doi: 10.1074/jbc.M112.344747
Wu Y, Hirschi KK. Regulation of hemogenic endothelial cell development and function. Annu Rev Physiol. 2021;83:17–37.
pubmed: 33035429
doi: 10.1146/annurev-physiol-021119-034352
Gritz E, Hirschi KK. Specification and function of hemogenic endothelium during embryogenesis. Cell Mol Life Sci. 2016;73(8):1547–67.
pubmed: 26849156
pmcid: 4805691
doi: 10.1007/s00018-016-2134-0
Driskill JH, Pan D. Control of stem cell renewal and fate by YAP and TAZ. Nat Rev Mol Cell Biol. 2023;24(12):895–911.
pubmed: 37626124
doi: 10.1038/s41580-023-00644-5
Qin H, Hejna M, Liu Y, Percharde M, Wossidlo M, Blouin L, et al. YAP induces human naive pluripotency. Cell Rep. 2016;14(10):2301–12.
pubmed: 26947063
pmcid: 4807727
doi: 10.1016/j.celrep.2016.02.036
Wang S, Zhou L, Ling L, Meng X, Chu F, Zhang S, et al. The crosstalk between Hippo-YAP pathway and innate immunity. Front Immunol. 2020;11:323.
pubmed: 32174922
pmcid: 7056731
doi: 10.3389/fimmu.2020.00323
Damkham N, Issaragrisil S, Lorthongpanich C. Role of YAP as a mechanosensing molecule in stem cells and stem cell-derived hematopoietic cells. Int J Mol Sci. 2022;23(23):14634.
pubmed: 36498961
pmcid: 9737411
doi: 10.3390/ijms232314634
Laowtammathron C, Lorthongpanich C, Jiamvoraphong N, Srisook P, Klaihmon P, Kheolamai P, et al. Role of YAP in hematopoietic differentiation and erythroid lineage specification of human-induced pluripotent stem cells. Stem Cell Res Ther. 2023;14(1):279.
pubmed: 37775798
pmcid: 10543272
doi: 10.1186/s13287-023-03508-z
Howard A, Bojko J, Flynn B, Bowen S, Jungwirth U, Walko G. Targeting the Hippo/YAP/TAZ signalling pathway: novel opportunities for therapeutic interventions into skin cancers. Exp Dermatol. 2022;31(10):1477–99.
pubmed: 35913427
pmcid: 9804452
doi: 10.1111/exd.14655
Goode DK, Obier N, Vijayabaskar MS, Lie ALM, Lilly AJ, Hannah R, et al. Dynamic gene regulatory networks drive hematopoietic specification and differentiation. Dev Cell. 2016;36(5):572–87.
pubmed: 26923725
pmcid: 4780867
doi: 10.1016/j.devcel.2016.01.024
Kim KM, Mura-Meszaros A, Tollot M, Krishnan MS, Grundl M, Neubert L, et al. Taz protects hematopoietic stem cells from an aging-dependent decrease in PU.1 activity. Nat Commun. 2022;13(1):5187.
pubmed: 36057685
pmcid: 9440927
doi: 10.1038/s41467-022-32970-1
de la Grange P, Jolly A, Courageux C, Ben Brahim C, Leroy P. Genes coding for transcription factors involved in stem cell maintenance are repressed by TGF-beta and downstream of Slug/Snail2 in COPD bronchial epithelial progenitors. Mol Biol Rep. 2021;48(10):6729–38.
pubmed: 34436724
doi: 10.1007/s11033-021-06664-8
Liu X, Ye Y, Zhu L, Xiao X, Zhou B, Gu Y, et al. Niche stiffness sustains cancer stemness via TAZ and NANOG phase separation. Nat Commun. 2023;14(1):238.
pubmed: 36646707
pmcid: 9842735
doi: 10.1038/s41467-023-35856-y