Discovery and Application of Postnatal Nucleus Pulposus Progenitors Essential for Intervertebral Disc Homeostasis and Degeneration
Abstract Intervertebral disc degeneration (IDD) results from the dysfunction of nucleus pulposus (NP) cells and the exhaustion of NP progenitors (ProNPs). The cellular applications of NP cells during IDD are currently limited due to the lack of in vivo studies showing whether NP cells are heterogene...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-05-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202104888 |
| _version_ | 1811234698364452864 |
|---|---|
| author | Bo Gao Bo Jiang Wenhui Xing Zaiqi Xie Zhuojing Luo Weiguo Zou |
| author_facet | Bo Gao Bo Jiang Wenhui Xing Zaiqi Xie Zhuojing Luo Weiguo Zou |
| author_sort | Bo Gao |
| collection | DOAJ |
| description | Abstract Intervertebral disc degeneration (IDD) results from the dysfunction of nucleus pulposus (NP) cells and the exhaustion of NP progenitors (ProNPs). The cellular applications of NP cells during IDD are currently limited due to the lack of in vivo studies showing whether NP cells are heterogeneous and contain ProNPs throughout postnatal stages. In this study, single‐cell RNA sequencing of purified NP cells is used to map four molecularly defined populations and urotensin II receptor (UTS2R)‐expressing postnatal ProNPs is identified, which are markedly exhausted during IDD, in mouse and human specimens. The lineage tracing shows that UTS2R+ ProNPs preferentially resides in the NP periphery with its niche factor tenascin‐C and give rise to functional NP cells. It is also demonstrated that transplanting UTS2R+ ProNPs with tenascin‐C into injured intervertebral discs attenuate the progression of IDD. The study provides a novel NP cell atlas, identified resident ProNPs with regenerative potential, and revealed promising diagnostic and therapeutic targets for IDD. |
| first_indexed | 2024-04-12T11:40:06Z |
| format | Article |
| id | doaj.art-b53395c4e8934cd685028eefedf5cacf |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-12T11:40:06Z |
| publishDate | 2022-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-b53395c4e8934cd685028eefedf5cacf2022-12-22T03:34:40ZengWileyAdvanced Science2198-38442022-05-01913n/an/a10.1002/advs.202104888Discovery and Application of Postnatal Nucleus Pulposus Progenitors Essential for Intervertebral Disc Homeostasis and DegenerationBo Gao0Bo Jiang1Wenhui Xing2Zaiqi Xie3Zhuojing Luo4Weiguo Zou5State Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell Sciences Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai ChinaState Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell Sciences Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai ChinaState Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell Sciences Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai ChinaState Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell Sciences Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai ChinaInstitute of Orthopaedic Surgery Xijing Hospital Air Force Military Medical University Xi'an Shaanxi ChinaState Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell Sciences Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai ChinaAbstract Intervertebral disc degeneration (IDD) results from the dysfunction of nucleus pulposus (NP) cells and the exhaustion of NP progenitors (ProNPs). The cellular applications of NP cells during IDD are currently limited due to the lack of in vivo studies showing whether NP cells are heterogeneous and contain ProNPs throughout postnatal stages. In this study, single‐cell RNA sequencing of purified NP cells is used to map four molecularly defined populations and urotensin II receptor (UTS2R)‐expressing postnatal ProNPs is identified, which are markedly exhausted during IDD, in mouse and human specimens. The lineage tracing shows that UTS2R+ ProNPs preferentially resides in the NP periphery with its niche factor tenascin‐C and give rise to functional NP cells. It is also demonstrated that transplanting UTS2R+ ProNPs with tenascin‐C into injured intervertebral discs attenuate the progression of IDD. The study provides a novel NP cell atlas, identified resident ProNPs with regenerative potential, and revealed promising diagnostic and therapeutic targets for IDD.https://doi.org/10.1002/advs.202104888intervertebral disclineage tracingnucleus pulposus cell atlasSc‐RNA seqstem cell therapy |
| spellingShingle | Bo Gao Bo Jiang Wenhui Xing Zaiqi Xie Zhuojing Luo Weiguo Zou Discovery and Application of Postnatal Nucleus Pulposus Progenitors Essential for Intervertebral Disc Homeostasis and Degeneration Advanced Science intervertebral disc lineage tracing nucleus pulposus cell atlas Sc‐RNA seq stem cell therapy |
| title | Discovery and Application of Postnatal Nucleus Pulposus Progenitors Essential for Intervertebral Disc Homeostasis and Degeneration |
| title_full | Discovery and Application of Postnatal Nucleus Pulposus Progenitors Essential for Intervertebral Disc Homeostasis and Degeneration |
| title_fullStr | Discovery and Application of Postnatal Nucleus Pulposus Progenitors Essential for Intervertebral Disc Homeostasis and Degeneration |
| title_full_unstemmed | Discovery and Application of Postnatal Nucleus Pulposus Progenitors Essential for Intervertebral Disc Homeostasis and Degeneration |
| title_short | Discovery and Application of Postnatal Nucleus Pulposus Progenitors Essential for Intervertebral Disc Homeostasis and Degeneration |
| title_sort | discovery and application of postnatal nucleus pulposus progenitors essential for intervertebral disc homeostasis and degeneration |
| topic | intervertebral disc lineage tracing nucleus pulposus cell atlas Sc‐RNA seq stem cell therapy |
| url | https://doi.org/10.1002/advs.202104888 |
| work_keys_str_mv | AT bogao discoveryandapplicationofpostnatalnucleuspulposusprogenitorsessentialforintervertebraldischomeostasisanddegeneration AT bojiang discoveryandapplicationofpostnatalnucleuspulposusprogenitorsessentialforintervertebraldischomeostasisanddegeneration AT wenhuixing discoveryandapplicationofpostnatalnucleuspulposusprogenitorsessentialforintervertebraldischomeostasisanddegeneration AT zaiqixie discoveryandapplicationofpostnatalnucleuspulposusprogenitorsessentialforintervertebraldischomeostasisanddegeneration AT zhuojingluo discoveryandapplicationofpostnatalnucleuspulposusprogenitorsessentialforintervertebraldischomeostasisanddegeneration AT weiguozou discoveryandapplicationofpostnatalnucleuspulposusprogenitorsessentialforintervertebraldischomeostasisanddegeneration |