Restoring mammary gland structures and functions with autogenous cell therapy

Zhang, Dandan; Wang, Guodong; Qin, Liangshan; Liu, Quanhui; Zhu, Shaoqian; Ye, Sheng; Li, Xiaobo; Wu, Yulian; Hu, Yanan; Liu, Shulin; Jiao, Yafei; Sun, Longfei; Lv, Danwei; Ma, Jiawen; Luo, Ming; Yao, Mengcheng; Li, Mengmei; Zhou, Lei; Pei, Surui; Li, Lanyu; Shi, Deshun; Huang, Bingqing

doi:10.1016/j.biomaterials.2021.121075

Cited by 6 publications

(12 citation statements)

References 35 publications

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“…In previous studies ( Zhang et al, 2021 ), we have clearly identified that RepSox is critical to the occurrence of CiMEC reprogramming and the lineage determination of reprogrammed cells. RepSox can widely inhibit the TGF-β expression of signal pathway-related genes.…”

Section: Discussionmentioning

confidence: 78%

“…Previously, we have demonstrated that efficient goat ear fibroblasts (GEFs) reprogrammed into chemically induced mammary epithelial cells (CiMECs) with lactation function can be accomplished by treatment with a cocktail of five small molecules [BFRTV, including TTNPB (B), forskolin (F), RepSox (R), tranylcypromine (T), and VPA (V)] ( Zhang et al, 2021 ). However, the molecular mechanisms and the lineage conversion process underlying BFRTV induction were not well understood, which limits the strategy optimization to increase the reprogramming efficiency.…”

Section: Introductionmentioning

confidence: 99%

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Dissecting the molecular trajectory of fibroblast reprogramming to chemically induced mammary epithelial cells

Qin

Zhang

Liu

et al. 2023

Front. Cell Dev. Biol.

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Introduction: The plasticity of cell identity allows cellular reprogramming that manipulates the lineage of cells to generate the target cell types, bringing new avenues for disease modeling and autologous tailored cell therapy. Previously, we had already successfully established a technical platform for inducing fibroblast reprogramming to chemically induced mammary epithelial cells (CiMECs) by small-molecule compounds. However, exactly how the molecular mechanism driving the lineage conversion remains unknown.Methods: We employ the RNA-sequencing technology to investigate the transcriptome event during the reprogramming process and reveal the molecular mechanisms for the fate acquisition of mammary lineage.Results: The multi-step reprogramming process first overcomes multiple barriers, including the inhibition of mesenchymal characteristics, pro-inflammatory and cell death signals, and then enters an intermediate plastic state. Subsequently, the hormone and mammary development genes were rapidly activated, leading to the acquisition of the mammary program together with upregulation of the milk protein synthesis signal. Moreover, the gene network analyses reveal the potential relationship between the TGF-β signaling pathway to mammary lineage activation, and the changes in the expression of these genes may play important roles in coordinating the reprogramming process.Conclusion: Together, these findings provide critical insights into the molecular route and mechanism triggered by small-molecule compounds that induce fibroblast reprogramming into the fate of mammary epithelial cells, and they also laid a foundation for the subsequent research on the development and differentiation of mammary epithelial cells and lactation.

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Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Dissecting the molecular trajectory of fibroblast reprogramming to chemically induced mammary epithelial cells

Qin

Zhang

Liu

et al. 2023

Front. Cell Dev. Biol.

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“…Our previous study 21 showed that a small chemical cocktail, BFRTV (B, TTNPB; F, forskolin; R, RepSox; T, tranylcypromine; and V, VPA), could induce fibroblasts to reprogram into mammary epithelial cells derived from the embryonic ectoderm. We then hypothesized that BFRTV might be able to induce the conversion of fibroblasts into other ectoderm-derived cells, such as neurons.…”

Section: Resultsmentioning

confidence: 99%

“…IF staining was performed as previously reported 6 , 21 . Cells were washed three times with PBS, fixed with 4% paraformaldehyde (PFA) for 20 min, and then blocked (in buffer containing 100 mmol/L glycine and 0.3% BSA in PBS) 3 times for 5 min each time.…”

Section: Methods Detailsmentioning

confidence: 99%

Forskolin-driven conversion of human somatic cells into induced neurons through regulation of the cAMP-CREB1-JNK signaling

Wang,

Zhang,

Qin

et al. 2024

Theranostics

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Human somatic cells can be reprogrammed into neuron cell fate through regulation of a single transcription factor or application of small molecule cocktails. Methods: Here, we report that forskolin efficiently induces the conversion of human somatic cells into induced neurons (FiNs). Results: A large population of neuron-like phenotype cells was observed as early as 24-36 h post-induction. There were >90% TUJ1-, >80% MAP2-, and >80% NEUN-positive neurons at 5 days post-induction. Multiple subtypes of neurons were present among TUJ1-positive cells, including >60% cholinergic, >20% glutamatergic, >10% GABAergic, and >5% dopaminergic neurons. FiNs exhibited typical neural electrophysiological activity in vitro and the ability to survive in vitro and in vivo more than 2 months. Mechanistically, forskolin functions in FiN reprogramming by regulating the cAMP-CREB1-JNK signals, which upregulates cAMP-CREB1 expression and downregulates JNK expression. Conclusion: Overall, our studies identify a safer and efficient single-small-molecule-driven reprogramming approach for induced neuron generation and reveal a novel regulatory mechanism of neuronal cell fate acquisition.

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“…Sequencing libraries were constructed according to a modified single-cell tagged reverse transcription (STRT) protocol as our previously reported 20 . In brief, after the samples were isolated, a 25 nucleotide (nt) oligo (dT) primer anchored with an 8 nt unique barcode and an 8 nt unique molecular identifiers (UMI) were added onto the RNA ends through reverse transcription.…”

Section: Scrna-seq Library Construction and Sequencingmentioning

confidence: 99%

Single-cell RNA-seq analysis reveals aberrant CSF1 expression in disease-causing synovial fibroblasts of pigmented villonodular synovitis

Tang

Moody

et al. 2021

Preprint

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Objectives: Although the role of the CSF1/CSF1R axis in pigmented villous synovitis (PVNS) has been confirmed, the cells that express CSF1 and CSF1R and the underlying mechanism remain unclear. Single-cell RNA sequencing (scRNA-seq) of PVNS obtained through biopsies depicted the cellular diversity of PVNS, revealed specific CSF1/CSF1R-expressing cells and further identified novel gene expression that is associated with the development of PVNS. Methods: scRNA-seq was performed on tissues obtained from the 6 biopsies of 3 patients with PVNS. Flow cytometry, immunofluorescence and western blot validated the transcriptional results, while co-culture systems revealed the cross talk between fibroblasts and macrophages. Results: 8 subsets of fibroblasts and 5 subsets of macrophages were identified from the synovium of patients with PVNS and were found to be related to distinct signaling pathways. The cellular components of localized and diffuse PVNS are overall similar. Moreover, the synovium and nodule of PVNS share similar composition. The specific cells expressing CSF1/CSF1R were also identified. Other than that, unique CXCL12+CSF1+ fibroblasts were revealed to attract macrophages as disease-causing synovial fibroblasts, leading to the formation of masses in PVNS. Conclusions: PVNS consists of macrophages, fibroblasts, T cells, endothelial cells and mast cells. Among them, the CSF1-expressing fibroblasts appeared to be tumor-like cells that attract macrophages, subsequently forming tumor-like mass in PVNS. This paves the path for novel treatments of PVNS by targeting CXCL12+CSF1+ fibroblasts and the CXCL12-CXCR4 axis.

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Restoring mammary gland structures and functions with autogenous cell therapy

Cited by 6 publications

References 35 publications

Dissecting the molecular trajectory of fibroblast reprogramming to chemically induced mammary epithelial cells

Dissecting the molecular trajectory of fibroblast reprogramming to chemically induced mammary epithelial cells

Forskolin-driven conversion of human somatic cells into induced neurons through regulation of the cAMP-CREB1-JNK signaling

Single-cell RNA-seq analysis reveals aberrant CSF1 expression in disease-causing synovial fibroblasts of pigmented villonodular synovitis

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