Trappc9 Deficiency Impairs the Plasticity of Stem Cells
Genetic mutations of <i>trappc9</i> cause intellectual disability with the atrophy of brain structures and variable obesity by poorly understood mechanisms. Trappc9-deficient mice develop phenotypes resembling pathological changes in humans and appear overweight shortly after weaning, an...
| Main Authors: | , , , , , , |
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| Format: | Article |
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Multidisciplinary Digital Publishing Institute
2022
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| Online Access: | https://hdl.handle.net/1721.1/142516 |
| _version_ | 1811094509699727360 |
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| author | Usman, Muhammad Li, Yan Ke, Yuting Chhetri, Gaurav Islam, Md Ariful Wang, Zejian Li, Xueyi |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Usman, Muhammad Li, Yan Ke, Yuting Chhetri, Gaurav Islam, Md Ariful Wang, Zejian Li, Xueyi |
| author_sort | Usman, Muhammad |
| collection | MIT |
| description | Genetic mutations of <i>trappc9</i> cause intellectual disability with the atrophy of brain structures and variable obesity by poorly understood mechanisms. Trappc9-deficient mice develop phenotypes resembling pathological changes in humans and appear overweight shortly after weaning, and thus are useful for studying the pathogenesis of obesity. Here, we investigated the effects of trappc9 deficiency on the proliferation and differentiation capacity of adipose-derived stem cells (ASCs). We isolated ASCs from mice before overweight was developed and found that trappc9-null ASCs exhibited signs of premature senescence and cell death. While the lineage commitment was retained, trappc9-null ASCs preferred adipogenic differentiation. We observed a profound accumulation of lipid droplets in adipogenic cells derived from trappc9-deficient ASCs and marked differences in the distribution patterns and levels of calcium deposited in osteoblasts obtained from trappc9-null ASCs. Biochemical studies revealed that trappc9 deficiency resulted in an upregulated expression of rab1, rab11, and rab18, and agitated autophagy in ASCs. Moreover, we found that the content of neural stem cells in both the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus vastly declined in trappc9-null mice. Collectively, our results suggest that obesity, as well as brain structure hypoplasia induced by the deficiency of trappc9, involves an impairment in the plasticity of stem cells. |
| first_indexed | 2024-09-23T16:01:27Z |
| format | Article |
| id | mit-1721.1/142516 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:01:27Z |
| publishDate | 2022 |
| publisher | Multidisciplinary Digital Publishing Institute |
| record_format | dspace |
| spelling | mit-1721.1/1425162023-03-24T20:27:43Z Trappc9 Deficiency Impairs the Plasticity of Stem Cells Usman, Muhammad Li, Yan Ke, Yuting Chhetri, Gaurav Islam, Md Ariful Wang, Zejian Li, Xueyi Massachusetts Institute of Technology. Department of Biological Engineering Genetic mutations of <i>trappc9</i> cause intellectual disability with the atrophy of brain structures and variable obesity by poorly understood mechanisms. Trappc9-deficient mice develop phenotypes resembling pathological changes in humans and appear overweight shortly after weaning, and thus are useful for studying the pathogenesis of obesity. Here, we investigated the effects of trappc9 deficiency on the proliferation and differentiation capacity of adipose-derived stem cells (ASCs). We isolated ASCs from mice before overweight was developed and found that trappc9-null ASCs exhibited signs of premature senescence and cell death. While the lineage commitment was retained, trappc9-null ASCs preferred adipogenic differentiation. We observed a profound accumulation of lipid droplets in adipogenic cells derived from trappc9-deficient ASCs and marked differences in the distribution patterns and levels of calcium deposited in osteoblasts obtained from trappc9-null ASCs. Biochemical studies revealed that trappc9 deficiency resulted in an upregulated expression of rab1, rab11, and rab18, and agitated autophagy in ASCs. Moreover, we found that the content of neural stem cells in both the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus vastly declined in trappc9-null mice. Collectively, our results suggest that obesity, as well as brain structure hypoplasia induced by the deficiency of trappc9, involves an impairment in the plasticity of stem cells. 2022-05-13T12:26:17Z 2022-05-13T12:26:17Z 2022-04-28 2022-05-12T19:35:55Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/142516 International Journal of Molecular Sciences 23 (9): 4900 (2022) PUBLISHER_CC http://dx.doi.org/10.3390/ijms23094900 Creative Commons Attribution https://creativecommons.org/licenses/by/4.0 application/pdf Multidisciplinary Digital Publishing Institute Multidisciplinary Digital Publishing Institute |
| spellingShingle | Usman, Muhammad Li, Yan Ke, Yuting Chhetri, Gaurav Islam, Md Ariful Wang, Zejian Li, Xueyi Trappc9 Deficiency Impairs the Plasticity of Stem Cells |
| title | Trappc9 Deficiency Impairs the Plasticity of Stem Cells |
| title_full | Trappc9 Deficiency Impairs the Plasticity of Stem Cells |
| title_fullStr | Trappc9 Deficiency Impairs the Plasticity of Stem Cells |
| title_full_unstemmed | Trappc9 Deficiency Impairs the Plasticity of Stem Cells |
| title_short | Trappc9 Deficiency Impairs the Plasticity of Stem Cells |
| title_sort | trappc9 deficiency impairs the plasticity of stem cells |
| url | https://hdl.handle.net/1721.1/142516 |
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