Hematopoietic cell differentiation from embryonic and induced pluripotent stem cells

Lim, Wai Feng; Inoue-Yokoo, Tomoko; Tan, Keai Sinn; Lai, Mei I; Sugiyama, Daisuke

doi:10.1186/scrt222

Cited by 96 publications

(62 citation statements)

References 88 publications

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“…In the early attempts to obtain HSCs in vitro, investigators tried to directly differentiate PSCs. 50,51 In some studies, hemogenic endothelial precursor cells were generated. These studies attempted to mimic developmental hematopoiesis during embryogenesis in vitro, with varied success.…”

Section: Tf Reprogramming Pscsmentioning

confidence: 99%

Converting cell fates: generating hematopoietic stem cells de novo via transcription factor reprogramming

Daniel¹,

Lemischka

Moore³

2016

Annals of the New York Academy of Sciences

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Even though all paradigms of stem cell therapy and regenerative medicine emerged from the study of hematopoietic stem cells (HSCs), our inability to generate these cells de novo or expand them in vitro persists. Initial efforts to obtain these cells began with the use of embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) technologies, but these strategies have yet to yield fully functional cells. Subsequently, more recent approaches involve transcription factor (TF) overexpression to reprogram PSCs and various somatic cells. The induction of pluripotency with just four TFs by Shinya Yamanaka informs our ability to convert cell fates, and demonstrates the feasibility of utilizing terminally differentiated cells to generate cells with multilineage potential. In this review, we discuss the recent efforts undertaken using TF-based reprogramming strategies to convert several cell types into HSCs.

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Section: Tf Reprogramming Pscsmentioning

confidence: 99%

Converting cell fates: generating hematopoietic stem cells de novo via transcription factor reprogramming

Daniel¹,

Lemischka

Moore³

2016

Annals of the New York Academy of Sciences

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“…Hematopoietic specification of iPSC follows embryonic development in some degree and involves induction of mesoderm, followed by a transition wave of endothelial to hematopoietic cell differentiation and the emergence of hematopoietic progenitors (Lim et al, 2013; Slukvin, 2013). We assessed differentiation of single cell-derived iPSC colonies in serum free media towards hematopoietic lineages by harvesting non adherent cells from the colony culture following the standardized hematopoietic induction scheme depicted in figure 2A.…”

Section: Resultsmentioning

confidence: 99%

“…Megakaryoid differentiation from iPSC is hampered by low purity of megakaryoid cells and lack of expansion ability. Although, lentiviral-mediated over-expression of megakaryoid (transcriptional) regulators may be incompatible with cellular products due to genomic integrations or re-activation of exogenous genes, it has been successfully used to improve megakaryoid specification and to increase megakaryoblast expansion (Lim et al, 2013; Moreau et al, 2016; Nakamura et al, 2014; Takayama et al, 2010). Moreau et.al.…”

Section: Discussionmentioning

confidence: 99%

“…used exogenous transcription factor expression of GATA1, FLI1 and TAL1 to generate pure MK with a yield of 1*10 5 cells within a long culture period of 90 days using a EB-base protocol (Moreau et al, 2016). Nakamura et al used c-MYC, BMI1, and BCL-XL over-expression to increase survival and proliferation of megakaryoblasts, but was dependent on a C3H10T1/2 feeder layer (Lim et al, 2013). Interestingly, our 2D approach, without any further genetic modification or feeder layer, resulted in 7*10 3 cells within 17 days and a mean megakaryoid purity of 74%.…”

Section: Discussionmentioning

confidence: 99%

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Efficient production of erythroid, megakaryoid and myeloid cells, using single cell-derived iPSC colony differentiation

Hansen

Varga

Aarts

et al. 2018

Preprint

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Hematopoietic differentiation of human induced pluripotent stem cells (iPSCs) provide opportunities not only for fundamental research and disease modelling/drug testing but also for large-scale production of blood effector cells for future clinical application. Although there are multiple ways to differentiate human iPSCs towards hematopoietic lineages, there is a need to develop reproducible and robust protocols. Here we introduce an efficient way to produce three major blood cell types using a standardized differentiation protocol that starts with a single hematopoietic initiation step. This system is feeder-free, avoids EB-formation, starts with a hematopoietic initiation step based on a novel single cell-derived iPSC colony differentiation and produces multi-potential progenitors within 8-10 days. Followed by lineage-specific growth factor supplementation these cells can be matured into well characterized erythroid, megakaryoid and myeloid cells with high-purity, without transcription factor overexpression or any kind of pre-purification step. This standardized differentiation system provides a simple platform to produce specific blood cells in a reproducible manner for hematopoietic development studies, disease modelling, drug testing and the potential for future therapeutic applications.HighlightsEfficient hematopoietic differentiation from single cell-derived iPSC coloniesReproducible feeder-free, monolayer differentiation system independent of iPSC lineProduction of erythroid, megakaryoid and myeloid cells with high-purityPlatform for hematopoietic developmental research and future clinical application

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“…Células-tronco embrionárias (CTE) são células pluripotentes estabelecidas da massa celular interna de embriões em estágio de blastocisto, e são capazes de autorrenovação e de dar origem aos três folhetos embrionários ectoderme, mesoderme e endoderme (LIM et al, 2013). As células-tronco de pluripotência induzida (iPSC) possuem propriedades semelhantes às células-tronco embrionárias, ou seja, a autorrenovação e a habilidade de se diferenciar em todas as células dos três folhetos embrionários.…”

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Geração de célulastronco/progenitoras hematopoéticas e progenitores eritroides a partir de células-tronco de pluripotência induzida derivadas de pacientes com anemia falciforme

Paes¹

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AGRADECIMENTOSAos meus pais, Rita e João Roberto, e meu irmão, Rodrigo, por me darem o exemplo de dedicação e trabalho, e o suporte e incentivo para a realização dos meus objetivos.Ao Pablo pelo companheirismo e por estar presente em todos os momentos, sejam eles de vitórias ou de superação das derrotas. À professora Virgínia Picanço e Castro pela oportunidade, confiança e orientação no desenvolvimento deste trabalho.Aos colegas do pela convivência e ajuda na realização deste trabalho. Em especial à Luiza por tudo que me ensinou, pelo auxílio no desenvolvimento teórico e prático deste trabalho.A todos os pesquisadores, alunos e funcionários do Hemocentro. Em especial à Patrícia Bonini e Camila Menezes pelo auxílio na elaboração de experimentos e análises por citometria de fluxo, e à Carmen Simão por estar sempre disposta a ajudar. À Faculdade de Medicina de Ribeirão Preto pelo conhecimento científico adquirido ao longo do curso de pós-graduação. À secretaria do programa pela ajuda com os assuntos burocráticos relacionados ao programa. À FAPESP (Processo número 2016/08373-9) pelo auxílio financeiro e incentivo à pesquisa.Aos membros da banca por se disponibilizarem a avaliar este trabalho. E a todos que não nomeei, mas estiveram envolvidos direta ou indiretamente no desenvolvimento deste trabalho. Palavras-chave: Diferenciação hematopoética. iPSC. Diferenciação eritroide. In vitro. Anemia falciforme. ABSTRACT PAES, Bárbara Cristina Martins Fernandes. Generation of hematopoietic stem/progenitor cells and erythroid progenitor cells from induced pluripotent stem cells derived from patients with sickle cell anemia. 2018. 111 f. Dissertação (Mestrado em Oncologia Clínica, Células-Tronco e Terapia Celular) -Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, 2018.Induced pluripotent stem cells (iPSC) are cells generated by reprogramming somatic cells, they have the potential for differentiation into all types of cells in the adult organism. The differentiation of patient-specific iPSC into hematopoietic cells is a way of studying hematopoiesis in disease models, such as sickle cell anemia, and is also essential for the development of therapies. The present study proposed the generation of hematopoietic stem/progenitor cells and erythroid progenitors from iPSC derived from patients with sickle cell anemia. Throughout the differentiation, hematopoietic and erythroid developments were monitored by colony forming cell assay and immunophenotypic analysis. In this study, we generated cells with characteristics of hematopoietic stem/progenitor cells, of CD34 + CD45 + and CD45 + CD43 + phenotypes, erythroid progenitors (CD36 + , CD71 + and CD235a + ), as well as the formation of hematopoietic colonies in culture in semi-solid medium. The iPSC line PBscd08 demonstrated greater potential for differentiation into hematopoietic and erythroid cells than the other cell lines evaluated. The iPSC line PBscd01, also generated from peripheral blood mononuclear cells (PBMC) from patients with sickle cell an...

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Hematopoietic cell differentiation from embryonic and induced pluripotent stem cells

Cited by 96 publications

References 88 publications

Converting cell fates: generating hematopoietic stem cells de novo via transcription factor reprogramming

Converting cell fates: generating hematopoietic stem cells de novo via transcription factor reprogramming

Efficient production of erythroid, megakaryoid and myeloid cells, using single cell-derived iPSC colony differentiation

Geração de célulastronco/progenitoras hematopoéticas e progenitores eritroides a partir de células-tronco de pluripotência induzida derivadas de pacientes com anemia falciforme

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