Fate erasure logic of gene networks underlying direct neuronal conversion of somatic cells by microRNAs
Summary: Neurogenic microRNAs 9/9∗ and 124 (miR-9/9∗-124) drive the direct reprogramming of human fibroblasts into neurons with the initiation of the fate erasure of fibroblasts. However, whether the miR-9/9∗-124 fate erasure logic extends to the neuronal conversion of other somatic cell types remai...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724015043 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841558855040892928 |
|---|---|
| author | Kitra Cates Luorongxin Yuan Yan Yang Andrew S. Yoo |
| author_facet | Kitra Cates Luorongxin Yuan Yan Yang Andrew S. Yoo |
| author_sort | Kitra Cates |
| collection | DOAJ |
| description | Summary: Neurogenic microRNAs 9/9∗ and 124 (miR-9/9∗-124) drive the direct reprogramming of human fibroblasts into neurons with the initiation of the fate erasure of fibroblasts. However, whether the miR-9/9∗-124 fate erasure logic extends to the neuronal conversion of other somatic cell types remains unknown. Here, we uncover that miR-9/9∗-124 induces neuronal conversion of multiple cell types: dura fibroblasts, astrocytes, smooth muscle cells, and pericytes. We reveal the cell-type-specific and pan-somatic gene network erasure induced by miR-9/9∗-124, including cell cycle, morphology, and proteostasis gene networks. Leveraging these pan-somatic gene networks, we predict upstream regulators that may antagonize somatic fate erasure. Among the predicted regulators, we identify TP53 (p53), whose inhibition is sufficient to enhance neuronal conversion even in post-mitotic cells. This study extends miR-9/9∗-124 reprogramming to alternate somatic cells, reveals the pan-somatic gene network fate erasure logic of miR-9/9∗-124, and shows a neurogenic role for p53 inhibition in the miR-9/9∗-124 signaling cascade. |
| format | Article |
| id | doaj-art-9a455d1943ea4a6eafea06b3254df29c |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-9a455d1943ea4a6eafea06b3254df29c2025-01-06T04:08:37ZengElsevierCell Reports2211-12472025-01-01441115153Fate erasure logic of gene networks underlying direct neuronal conversion of somatic cells by microRNAsKitra Cates0Luorongxin Yuan1Yan Yang2Andrew S. Yoo3Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Program in Molecular Genetics and Genomics, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USADepartment of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Program in Molecular Genetics and Genomics, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Corresponding authorSummary: Neurogenic microRNAs 9/9∗ and 124 (miR-9/9∗-124) drive the direct reprogramming of human fibroblasts into neurons with the initiation of the fate erasure of fibroblasts. However, whether the miR-9/9∗-124 fate erasure logic extends to the neuronal conversion of other somatic cell types remains unknown. Here, we uncover that miR-9/9∗-124 induces neuronal conversion of multiple cell types: dura fibroblasts, astrocytes, smooth muscle cells, and pericytes. We reveal the cell-type-specific and pan-somatic gene network erasure induced by miR-9/9∗-124, including cell cycle, morphology, and proteostasis gene networks. Leveraging these pan-somatic gene networks, we predict upstream regulators that may antagonize somatic fate erasure. Among the predicted regulators, we identify TP53 (p53), whose inhibition is sufficient to enhance neuronal conversion even in post-mitotic cells. This study extends miR-9/9∗-124 reprogramming to alternate somatic cells, reveals the pan-somatic gene network fate erasure logic of miR-9/9∗-124, and shows a neurogenic role for p53 inhibition in the miR-9/9∗-124 signaling cascade.http://www.sciencedirect.com/science/article/pii/S2211124724015043CP: Stem cell researchCP: Molecular biology |
| spellingShingle | Kitra Cates Luorongxin Yuan Yan Yang Andrew S. Yoo Fate erasure logic of gene networks underlying direct neuronal conversion of somatic cells by microRNAs Cell Reports CP: Stem cell research CP: Molecular biology |
| title | Fate erasure logic of gene networks underlying direct neuronal conversion of somatic cells by microRNAs |
| title_full | Fate erasure logic of gene networks underlying direct neuronal conversion of somatic cells by microRNAs |
| title_fullStr | Fate erasure logic of gene networks underlying direct neuronal conversion of somatic cells by microRNAs |
| title_full_unstemmed | Fate erasure logic of gene networks underlying direct neuronal conversion of somatic cells by microRNAs |
| title_short | Fate erasure logic of gene networks underlying direct neuronal conversion of somatic cells by microRNAs |
| title_sort | fate erasure logic of gene networks underlying direct neuronal conversion of somatic cells by micrornas |
| topic | CP: Stem cell research CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724015043 |
| work_keys_str_mv | AT kitracates fateerasurelogicofgenenetworksunderlyingdirectneuronalconversionofsomaticcellsbymicrornas AT luorongxinyuan fateerasurelogicofgenenetworksunderlyingdirectneuronalconversionofsomaticcellsbymicrornas AT yanyang fateerasurelogicofgenenetworksunderlyingdirectneuronalconversionofsomaticcellsbymicrornas AT andrewsyoo fateerasurelogicofgenenetworksunderlyingdirectneuronalconversionofsomaticcellsbymicrornas |