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Chemical reprogramming of human blood cells into hCiPS cells

ABSTRACT: Chemical reprogramming of human blood cells into hCiPS cells

PROVIDER: PRJNA1284192 | ENA |

REPOSITORIES: ENA

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Chemical reprogramming of human blood cells into hCiPS cells

Project description:Chemical reprogramming offers a fundamentally innovative approach for generating human pluripotent stem (hCiPS) cells using small molecules. Our recent studies showed that this approach was highly efficient in reprogramming human fibroblasts to hCiPS cells. In this study, we established a robust method that successfully generated hCiPS cells from both cord blood and adult peripheral blood cells. This method achieved efficient reprogramming with both fresh and cryopreserved blood cells.

2025-07-30 | GSE301149 | GEO

Chemical reprogramming of human blood cells into hCiPS cells [scRNA-seq]

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Efficient Chemical Reprogramming of Human T Cells into Functional Megakaryocytes and Platelets

Project description:The generation of megakaryocytes (MKs) from human somatic cells through chemical reprogramming represents a promising strategy for developing alternative platelet sources. Building on our prior chemical reprogramming protocol for converting erythroblasts to MKs, we established a robust method that successfully generated induced MKs (iMKs) from human cord blood-derived CD3⁺ T cells, which is a more abundant source. This method utilized a five- small-molecule (5M) cocktail containing a reprogramming booster, AZD4205, to promote erasure of T cell identity and facilitate fate transition towards MKs. T cell-derived iMKs exhibited characteristic MK cellular and molecular signatures, demonstrating the capacity to produce proplatelets and release functional platelets in vitro and in vivo. ScRNA-sequencing further revealed that iMKs were heterogeneous with distinct functional profiles, including cycling, immune, and thrombopoiesis-biased MKs. Our findings highlight an optimized chemical reprogramming pathway that enables efficient conversion of T cells to MKs, providing a practical and convenient approach to generate clinically relevant MKs and platelets.

2025-11-27 | GSE310060 | GEO

Direct chemical reprogramming of human cord blood erythroblasts to induced megakaryocytes that produce platelets

Project description:The shortage of platelets is becoming increasingly prominent owing to their short shelf life, limited supply, and increasing demand in response to public health incidents. It is an attractive idea to obtain large numbers of transfusible megakaryocytes (MKs) and platelets from somatic cells via cell lineage reprogramming. However, generating human MKs from somatic cells using a pharmacological reprogramming approach has not been widely explored. Here, we report the successful generation of human induced MKs (iMKs) from cord blood erythroblasts (EBs) using a chemical reprogramming strategy with a combination of four small molecules (4M): Bix01294, RG108, VPA, and PD0325901. The iMKs exhibited the ability to produce proplatelets and release vital functional platelets in vitro, demonstrating their similarity to natural MKs. Importantly, after injection into mice, iMKs were able to mature and give rise to functional platelets that were incorporated into newly formed thrombi. The reprogramming process was carefully examined using single-cell RNA sequencing, which revealed an efficient, rapid, and successful cell fate conversion of EBs to iMKs by 4M via the intermediate state of bipotent precursors. Assay for transposase-accessible chromatin sequencing results indicated that 4M induced genome-wide chromatin remodeling during MK reprogramming from EBs. 4M drove the transition of the transcription factor gene network by downregulating the key erythroid transcription factor genes KLF1 and MYB and subsequently upregulating MK development-associated transcription factor genes, including FLI1 and MEIS1. This process eventually led human cord blood EBs to acquire the MK fate. Thus, our chemical reprogramming of cord blood EBs to iMKs provides a simple and efficient approach to generating clinically transfusible MKs and platelets.

2022-08-28 | GSE207654 | GEO

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