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Peer-reviewedCC BY 4.0PLOS One

Omicron SARS-CoV-2 shows NRP1-linked susceptibility in adipose-derived MSCs and alters primitive cord blood CD34⁺ HSPCs

  • Kanit Bhukhai1
  • Nopmullee Tanhuad2
  • Pornprapa Srimorkun3
  • Suwimon Manopwisedjaroen4
  • Wittaya Panvongsa5
  • Vimvara Vacharathit6
  • Phongthon Kanjanasirirat7
  • Umnuaychoke Thongsa-ad8
  • Supasek Kongsomros9
  • Nareerat Sutjarit10
  • Chanya Srisaowakarn11
  • Tulyapruek Tawonsawatruk
8 more authors
  • Patompon Wongtrakoongate
  • Nittaya Boonmuen
  • Suparerk Borwornpinyo
  • Usanarat Anurathapan
  • Arthit Chairoungdua
  • Nithi Asavapanumas
  • Suradej Hongeng
  • Arunee Thitithanyanont
11 affiliations
  1. 1Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand
  2. 2Department of Microbiology, Faculty of Science, Mahidol University, Thailand
  3. 3Department of Tropical Nutrition and Food Science, Faculty of Tropical Medicine, Mahidol University, Thailand
  4. 4Single-cell Omics and Systems Biology of Diseases (scSyBiD) Research Unit, Faculty of Science, Mahidol University, Bangkok, Thailand
  5. 5Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand
  6. 6Graduate Program in Nutrition, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Thailand
  7. 7Department of Orthopaedics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  8. 8Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand
  9. 9Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, Thailand
  10. 10Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  11. 11Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand
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Abstract

SARS-CoV-2 infection is linked to hematologic abnormalities, but whether early hematopoietic compartments and their stromal niche are directly engaged remains unclear. We used in vitro exposure models to compare variant-associated responses of adult mesenchymal stromal cells (MSCs) and umbilical cord blood (UCB) CD34 ⁺ hematopoietic stem and progenitor cells (HSPCs). Adipose–derived (AD) and bone marrow–derived (BM) MSCs exposed to wild-type, Delta, or Omicron showed source- and variant-dependent nucleocapsid protein (NP) positivity, highest with Omicron in AD-MSCs; infectious virus in supernatants was undetectable. AD-MSCs expressed higher neuropilin-1 (NRP1) than BM-MSCs, and NRP1 knockdown reduced Omicron-associated NP signal, implicating an NRP1-linked entry process. SARS-CoV-2 exposure induced indoleamine-2,3-dioxygenase 1 (IDO1), most prominently in AD-MSCs. In UCB CD34 ⁺ HSPCs, Omicron increased NP positivity enriched in long-term HSCs, reduced primitive fraction frequencies, increased colony formation, and promoted early erythroid progenitor accumulation; heat-inactivated virus did not. NanoString profiling revealed host-response activation and altered cell-cycle/differentiation programs. These data indicate Omicron can engage stromal and early hematopoietic compartments and remodel stress-responsive hematopoiesis.

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Cite

BibTeXRIS
BibTeX
@article{bhukhai2026omicron,
  title = {{Omicron SARS-CoV-2 shows NRP1-linked susceptibility in adipose-derived MSCs and alters primitive cord blood CD34⁺ HSPCs}},
  author = {Kanit Bhukhai and Nopmullee Tanhuad and Pornprapa Srimorkun and Suwimon Manopwisedjaroen and Wittaya Panvongsa and Vimvara Vacharathit and Phongthon Kanjanasirirat and Umnuaychoke Thongsa-ad and Supasek Kongsomros and Nareerat Sutjarit and Chanya Srisaowakarn and Tulyapruek Tawonsawatruk and Patompon Wongtrakoongate and Nittaya Boonmuen and Suparerk Borwornpinyo and Usanarat Anurathapan and Arthit Chairoungdua and Nithi Asavapanumas and Suradej Hongeng and Arunee Thitithanyanont},
  journal = {PLOS One},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.pone.0360439},
  url = {https://doi.org/10.1371/journal.pone.0360439},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Omicron SARS-CoV-2 shows NRP1-linked susceptibility in adipose-derived MSCs and alters primitive cord blood CD34⁺ HSPCs
AU  - Kanit Bhukhai
AU  - Nopmullee Tanhuad
AU  - Pornprapa Srimorkun
AU  - Suwimon Manopwisedjaroen
AU  - Wittaya Panvongsa
AU  - Vimvara Vacharathit
AU  - Phongthon Kanjanasirirat
AU  - Umnuaychoke Thongsa-ad
AU  - Supasek Kongsomros
AU  - Nareerat Sutjarit
AU  - Chanya Srisaowakarn
AU  - Tulyapruek Tawonsawatruk
AU  - Patompon Wongtrakoongate
AU  - Nittaya Boonmuen
AU  - Suparerk Borwornpinyo
AU  - Usanarat Anurathapan
AU  - Arthit Chairoungdua
AU  - Nithi Asavapanumas
AU  - Suradej Hongeng
AU  - Arunee Thitithanyanont
PY  - 2026
DA  - 2026/10/12
JO  - PLOS One
DO  - 10.1371/journal.pone.0360439
UR  - https://doi.org/10.1371/journal.pone.0360439
AB  - SARS-CoV-2 infection is linked to hematologic abnormalities, but whether early hematopoietic compartments and their stromal niche are directly engaged remains unclear. We used in vitro exposure models to compare variant-associated responses of adult mesenchymal stromal cells (MSCs) and umbilical cord blood (UCB) CD34 ⁺ hematopoietic stem and progenitor cells (HSPCs). Adipose–derived (AD) and bone marrow–derived (BM) MSCs exposed to wild-type, Delta, or Omicron showed source- and variant-dependent nucleocapsid protein (NP) positivity, highest with Omicron in AD-MSCs; infectious virus in supernatants was undetectable. AD-MSCs expressed higher neuropilin-1 (NRP1) than BM-MSCs, and NRP1 knockdown reduced Omicron-associated NP signal, implicating an NRP1-linked entry process. SARS-CoV-2 exposure induced indoleamine-2,3-dioxygenase 1 (IDO1), most prominently in AD-MSCs. In UCB CD34 ⁺ HSPCs, Omicron increased NP positivity enriched in long-term HSCs, reduced primitive fraction frequencies, increased colony formation, and promoted early erythroid progenitor accumulation; heat-inactivated virus did not. NanoString profiling revealed host-response activation and altered cell-cycle/differentiation programs. These data indicate Omicron can engage stromal and early hematopoietic compartments and remodel stress-responsive hematopoiesis.
SN  - 1932-6203
ER  -