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Article: Cancer associated fibroblasts serve as an ovarian cancer stem cell niche through noncanonical Wnt5a signaling.

Fang, Yiming / Xiao, Xue / Wang, Ji / Dasari, Subramanyam / Pepin, David / Nephew, Kenneth P / Zamarin, Dmitriy / Mitra, Anirban K

NPJ precision oncology

2024 Volume 8, Issue 1, Page(s) 7

Abstract: Frequent relapse and chemoresistance cause poor outcome in ovarian cancer (OC) and cancer stem cells (CSCs) are important contributors. While most studies focus exclusively on CSCs, the role of the microenvironment in providing optimal conditions to ... ...

Abstract	Frequent relapse and chemoresistance cause poor outcome in ovarian cancer (OC) and cancer stem cells (CSCs) are important contributors. While most studies focus exclusively on CSCs, the role of the microenvironment in providing optimal conditions to maintain their tumor-initiating potential remains poorly understood. Cancer associated fibroblasts (CAFs) are a major constituent of the OC tumor microenvironment and we show that CAFs and CSCs are enriched following chemotherapy in patient tumors. CAFs significantly increase OC cell resistance to carboplatin. Using heterotypic CAF-OC cocultures and in vivo limiting dilution assay, we confirm that the CAFs act by enriching the CSC population. CAFs increase the symmetric division of CSCs as well as the dedifferentiation of bulk OC cells into CSCs. The effect of CAFs is limited to OC cells in their immediate neighborhood, which can be prevented by inhibiting Wnt. Analysis of single cell RNA-seq data from OC patients reveal Wnt5a as the highest expressed Wnt in CAFs and that certain subpopulations of CAFs express higher levels of Wnt5a. Our findings demonstrate that Wnt5a from CAFs activate a noncanonical Wnt signaling pathway involving the ROR2/PKC/CREB1 axis in the neighboring CSCs. While canonical Wnt signaling is found to be predominant in interactions between cancer cells in patients, non-canonical Wnt pathway is activated by the CAF-OC crosstalk. Treatment with a Wnt5a inhibitor sensitizes tumors to carboplatin in vivo. Together, our results demonstrate a novel mechanism of CSC maintenance by signals from the microenvironmental CAFs, which can be targeted to treat OC chemoresistance and relapse.
Language	English
Publishing date	2024-01-08
Publishing country	England
Document type	Journal Article
ISSN	2397-768X
ISSN	2397-768X
DOI	10.1038/s41698-023-00495-5
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Article ; Online: Lats1 and Lats2 regulate YAP and TAZ activity to control the development of mouse Sertoli cells.

Abou Nader, Nour / Charrier, Laureline / Meisnsohn, Marie-Charlotte / Banville, Laurence / Deffrennes, Bérengère / St-Jean, Guillaume / Boerboom, Derek / Zamberlam, Gustavo / Brind'Amour, Julie / Pépin, David / Boyer, Alexandre

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2024 Volume 38, Issue 9, Page(s) e23633

Abstract: Recent reports suggest that the Hippo signaling pathway regulates testis development, though its exact roles in Sertoli cell differentiation remain unknown. Here, we examined the functions of the main Hippo pathway kinases, large tumor suppressor homolog ...

Abstract	Recent reports suggest that the Hippo signaling pathway regulates testis development, though its exact roles in Sertoli cell differentiation remain unknown. Here, we examined the functions of the main Hippo pathway kinases, large tumor suppressor homolog kinases 1 and 2 (Lats1 and Lats2) in developing mouse Sertoli cells. Conditional inactivation of Lats1/2 in Sertoli cells resulted in the disorganization and overgrowth of the testis cords, the induction of a testicular inflammatory response and germ cell apoptosis. Stimulated by retinoic acid 8 (STRA8) expression in germ cells additionally suggested that germ cells may have been preparing to enter meiosis prior to their loss. Gene expression analyses of the developing testes of conditional knockout animals further suggested impaired Sertoli cell differentiation, epithelial-to-mesenchymal transition, and the induction of a specific set of genes associated with Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ)-mediated integrin signaling. Finally, the involvement of YAP/TAZ in Sertoli cell differentiation was confirmed by concomitantly inactivating Yap/Taz in Lats1/2 conditional knockout model, which resulted in a partial rescue of the testicular phenotypic changes. Taken together, these results identify Hippo signaling as a crucial pathway for Sertoli cell development and provide novel insight into Sertoli cell fate maintenance.
MeSH term(s)	Animals ; Sertoli Cells/metabolism ; Protein Serine-Threonine Kinases/metabolism ; Protein Serine-Threonine Kinases/genetics ; Male ; Mice ; YAP-Signaling Proteins/metabolism ; Adaptor Proteins, Signal Transducing/metabolism ; Adaptor Proteins, Signal Transducing/genetics ; Tumor Suppressor Proteins/metabolism ; Tumor Suppressor Proteins/genetics ; Cell Differentiation/physiology ; Mice, Knockout ; Signal Transduction ; Cell Cycle Proteins/metabolism ; Cell Cycle Proteins/genetics ; Testis/metabolism ; Epithelial-Mesenchymal Transition/physiology ; Transcription Factors/metabolism ; Transcription Factors/genetics ; Acyltransferases/genetics ; Acyltransferases/metabolism ; Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism ; Trans-Activators/metabolism ; Trans-Activators/genetics
Chemical Substances	Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Lats1 protein, mouse (EC 2.7.1.-) ; LATS2 protein, mouse (EC 2.7.11.1) ; YAP-Signaling Proteins ; Adaptor Proteins, Signal Transducing ; Yap1 protein, mouse ; Tumor Suppressor Proteins ; Wwtr1 protein, mouse ; Cell Cycle Proteins ; tafazzin protein, mouse (EC 2.3.-) ; Transcription Factors ; Acyltransferases (EC 2.3.-) ; Transcriptional Coactivator with PDZ-Binding Motif Proteins ; Trans-Activators ; Stra8 protein, mouse
Language	English
Publishing date	2024-04-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202400346R
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Article: Structural Basis of Non-Latent Signaling by the Anti-Müllerian Hormone Procomplex.

Howard, James A / Hok, Lucija / Cate, Richard L / Sanford, Nathaniel J / Hart, Kaitlin N / Leach, Edmund Ae / Bruening, Alena S / Pépin, David / Donahoe, Patricia K / Thompson, Thomas B

bioRxiv : the preprint server for biology

2024

Abstract: Most TGFβ family ligands exist as procomplexes consisting of a prodomain noncovalently bound to a growth factor (GF); Whereas some prodomains confer latency, the Anti-Müllerian Hormone (AMH) prodomain maintains a remarkably high affinity for the GF yet ... ...

Abstract	Most TGFβ family ligands exist as procomplexes consisting of a prodomain noncovalently bound to a growth factor (GF); Whereas some prodomains confer latency, the Anti-Müllerian Hormone (AMH) prodomain maintains a remarkably high affinity for the GF yet remains active. Using single particle EM methods, we show the AMH prodomain consists of two subdomains: a vestigial TGFβ prodomain-like fold and a novel, helical bundle GF-binding domain, the result of an exon insertion 450 million years ago, that engages both receptor epitopes. When associated with the prodomain, the AMH GF is distorted into a strained, open conformation whose closure upon bivalent binding of AMHR2 displaces the prodomain through a conformational shift mechanism to allow for signaling.
Language	English
Publishing date	2024-04-01
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.04.01.587627
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Article ; Online: A genome-wide strategy to identify causes and consequences of retrotransposon expression finds activation by BRCA1 in ovarian cancer.

Alkailani, Maisa / Palidwor, Gareth / Poulin, Ariane / Mohan, Raghav / Pepin, David / Vanderhyden, Barbara / Gibbings, Derrick

NAR cancer

2021 Volume 3, Issue 1, Page(s) zcaa040

Abstract: It is challenging to identify the causes and consequences of retrotransposon expression in human disease due to the hundreds of active genomic copies and their poor conservation across species. We profiled genomic insertions of retrotransposons in ... ...

Abstract	It is challenging to identify the causes and consequences of retrotransposon expression in human disease due to the hundreds of active genomic copies and their poor conservation across species. We profiled genomic insertions of retrotransposons in ovarian cancer. In addition, in ovarian and breast cancer we analyzed RNAs exhibiting Bayesian correlation with retrotransposon RNA to identify causes and consequences of retrotransposon expression. This strategy finds divergent inflammatory responses associated with retrotransposon expression in ovarian and breast cancer and identifies new factors inducing expression of endogenous retrotransposons including anti-viral responses and the common tumor suppressor BRCA1. In cell lines, mouse ovarian epithelial cells and patient-derived tumor spheroids, BRCA1 promotes accumulation of retrotransposon RNA. BRCA1 promotes transcription of active families of retrotransposons and their insertion into the genome. Intriguingly, elevated retrotransposon expression predicts survival in ovarian cancer patients. Retrotransposons are part of a complex regulatory network in ovarian cancer including BRCA1 that contributes to patient survival. The described strategy can be used to identify the regulators and impacts of retrotransposons in various contexts of biology and disease in humans.
Language	English
Publishing date	2021-01-06
Publishing country	England
Document type	Journal Article
ISSN	2632-8674
ISSN (online)	2632-8674
DOI	10.1093/narcan/zcaa040
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Article ; Online: Blocking estrogen-induced AMH expression is crucial for normal follicle formation.

Tanimoto, Ren / Sekii, Kiyono / Morohaku, Kanako / Li, Jianzhen / Pépin, David / Obata, Yayoi

Development (Cambridge, England)

2021 Volume 148, Issue 6

Abstract: In mammals, primordial follicles assembled in fetuses or during infancy constitute the oocyte resources for life. Exposure to 17beta-estradiol and phytogenic or endocrine-disrupting chemicals during pregnancy and/or the perinatal period leads to the ... ...

Abstract	In mammals, primordial follicles assembled in fetuses or during infancy constitute the oocyte resources for life. Exposure to 17beta-estradiol and phytogenic or endocrine-disrupting chemicals during pregnancy and/or the perinatal period leads to the failure of normal follicle formation. However, the mechanisms underlying estrogen-mediated abnormal follicle formation and physiological follicle formation in the presence of endogenous natural estrogen are not well understood. Here, we reveal that estrogen receptor 1, activated by estrogen, binds to the 5' region of the anti-Mullerian hormone (
MeSH term(s)	Animals ; Anti-Mullerian Hormone/genetics ; Endocrine Disruptors/toxicity ; Estradiol/pharmacology ; Estrogen Receptor alpha/genetics ; Estrogens/genetics ; Estrogens/metabolism ; Female ; Humans ; Mice ; Oocytes/growth & development ; Ovarian Follicle/growth & development ; Ovarian Follicle/metabolism ; Transcription, Genetic/genetics ; alpha-Fetoproteins/genetics
Chemical Substances	Endocrine Disruptors ; Estrogen Receptor alpha ; Estrogens ; alpha-Fetoproteins ; Estradiol (4TI98Z838E) ; Anti-Mullerian Hormone (80497-65-0)
Language	English
Publishing date	2021-03-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.197459
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Article ; Online: Müllerian inhibiting substance/anti-Müllerian hormone as a fertility preservation agent.

Pépin, David / Sabatini, Mary E / Donahoe, Patricia K

Current opinion in endocrinology, diabetes, and obesity

2018 Volume 25, Issue 6, Page(s) 399–405

Abstract: Purpose of review: The nascent field of oncofertility is quickly gaining traction as novel experimental treatments are being developed, driving a renewed interest in Müllerian inhibiting substance (MIS) as an ovarian fertoprotectant.: Recent findings!# ...

Abstract	Purpose of review: The nascent field of oncofertility is quickly gaining traction as novel experimental treatments are being developed, driving a renewed interest in Müllerian inhibiting substance (MIS) as an ovarian fertoprotectant. Recent findings: MIS is unique in its mechanisms of ovarian protection by virtue of acting directly on granulosa cells of primordial follicles and for being a benign reproductive hormone, with few side effects. We will explore in this review how it may be utilized to protect the ovary from chemotherapy, or to enhance ovarian tissue cryopreservation therapy. We will also examine potential mechanisms of action of MIS across multiple cell types, as well as current limitations in our understanding of the pharmacology of recombinant MIS. Summary: The usefulness of MIS as a fertoprotectant may be dependent on the mechanisms of gonadotoxicity of each chemotherapeutic. Further investigation is needed to determine how to best deliver and combine MIS treatment to existing fertility management strategies.
MeSH term(s)	Anti-Mullerian Hormone/physiology ; Anti-Mullerian Hormone/therapeutic use ; Cryopreservation/methods ; Female ; Fertility Agents, Female/therapeutic use ; Fertility Preservation/methods ; Granulosa Cells/drug effects ; Granulosa Cells/physiology ; Humans ; Ovarian Follicle/drug effects ; Ovarian Follicle/physiology ; Ovary
Chemical Substances	Fertility Agents, Female ; Anti-Mullerian Hormone (80497-65-0)
Language	English
Publishing date	2018-10-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2272017-0
ISSN	1752-2978 ; 1752-296X
ISSN (online)	1752-2978
ISSN	1752-296X
DOI	10.1097/MED.0000000000000442
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Article ; Online: Mutational Analysis of the Putative Anti-Müllerian Hormone (AMH) Binding Interface on its Type II Receptor, AMHR2.

Hart, Kaitlin N / Pépin, David / Czepnik, Magdalena / Donahoe, Patricia K / Thompson, Thomas B

Endocrinology

2020 Volume 161, Issue 7

Abstract: Anti-Müllerian hormone (AMH) or Müllerian inhibiting substance is a unique member of the TGF-β family responsible for development and differentiation of the reproductive system. AMH signals through its own dedicated type II receptor, anti-Müllerian ... ...

Abstract	Anti-Müllerian hormone (AMH) or Müllerian inhibiting substance is a unique member of the TGF-β family responsible for development and differentiation of the reproductive system. AMH signals through its own dedicated type II receptor, anti-Müllerian hormone receptor type II (AMHR2), providing an exclusive ligand-receptor pair within the broader TGF-β family. In this study, we used previous structural information to derive a model of AMH bound to AMHR2 to guide mutagenesis studies to identify receptor residues important for AMH signaling. Nonconserved mutations were introduced in AMHR2 and characterized in an AMH-responsive cell-based luciferase assay and native PAGE. Collectively, our results identified several residues important for AMH signaling within the putative ligand binding interface of AMHR2. Our results show that AMH engages AMHR2 at a similar interface to how activin and BMP class ligands bind the type II receptor, ACVR2B; however, there are significant molecular differences at the ligand interface of these 2 receptors, where ACVR2B is mostly hydrophobic and AMHR2 is predominately charged. Overall, this study shows that although the location of ligand binding on the receptor is similar to ACVR2A, ACVR2B, and BMPR2; AMHR2 uses unique ligand-receptor interactions to impart specificity for AMH.
MeSH term(s)	Activin Receptors, Type II/chemistry ; Activin Receptors, Type II/metabolism ; Anti-Mullerian Hormone/metabolism ; Disorder of Sex Development, 46,XY/genetics ; HEK293 Cells ; Humans ; Mutagenesis, Site-Directed ; Receptors, Peptide/chemistry ; Receptors, Peptide/genetics ; Receptors, Peptide/metabolism ; Receptors, Transforming Growth Factor beta/chemistry ; Receptors, Transforming Growth Factor beta/genetics ; Receptors, Transforming Growth Factor beta/metabolism
Chemical Substances	Receptors, Peptide ; Receptors, Transforming Growth Factor beta ; anti-Mullerian hormone receptor ; Anti-Mullerian Hormone (80497-65-0) ; ACVR2B protein, human (EC 2.7.11.30) ; Activin Receptors, Type II (EC 2.7.11.30)
Language	English
Publishing date	2020-05-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/endocr/bqaa066
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Article ; Online: An ovarian phenotype of alpha 7 nicotinic receptor knockout mice.

Seßenhausen, Pia / Caban, Karolina M / Kreitmair, Nicole / Peitzsch, Mirko / Stöckl, Jan B / Meinsohn, Marie C / Pépin, David / Popper, Bastian / Fröhlich, Thomas / Mayerhofer, Artur

Reproduction (Cambridge, England)

2023 Volume 166, Issue 3, Page(s) 221–234

Abstract: In brief: Nicotinic acetylcholine receptor alpha 7 (nAChRa7), encoded by Chrna7, is expressed by various murine ovarian cells. Morphological and molecular investigations, including a proteomic study of adult Chrna7 knockout (KO) mouse ovaries, reveal ... ...

Abstract	In brief: Nicotinic acetylcholine receptor alpha 7 (nAChRa7), encoded by Chrna7, is expressed by various murine ovarian cells. Morphological and molecular investigations, including a proteomic study of adult Chrna7 knockout (KO) mouse ovaries, reveal the roles of these receptors in the local regulation of the ovary. Abstract: Nicotinic acetylcholine receptor alpha 7 (nAChRa7), encoded by Chrna7, is involved in cellular functions ranging from synaptic transmission in neurons to regulation of inflammation, cell growth and metabolism to cell death in other cells. Our qPCR results and other studies indicated that nAChRa7 is expressed in the adult mouse ovary, while in situ hybridization and single-cell sequencing data suggested this expression may be shared by several ovarian cells, including fibroblast-like and steroidogenic stroma cells, macrophages and oocytes of small follicles. To explore a possible involvement of nAChRa7 in ovarian functions, we evaluated ovarian morphology of Chrna7-null mutant adult mice (KO) and wildtype mice (WT; 3 months, metestrus) by performing immunohistochemistry, qPCR studies, measurements of serum progesterone and proteomic analyses. The evaluation of serial sections indicated fewer primordial follicles but similar numbers of primary, secondary and tertiary follicles, as well as corpora lutea in KO and WT mice. Atresia was unchanged. Serum progesterone and mRNA levels of proliferation and most apoptosis markers were not changed, yet two typical macrophage markers were elevated. Furthermore, the proteomes of KO ovaries were significantly altered with 96 proteins increased and 32 decreased in abundance in KOs compared to WTs. Among the elevated proteins were markers for stroma cells. Hence, the lack of nAChRa7 causes changes in small follicle counts and alterations of the ovarian stroma cells. The ovarian phenotype of Chrna7 mutant mice links this channel protein to the local regulation of ovarian cells, including stroma cells.
MeSH term(s)	Animals ; Female ; Mice ; Mice, Knockout ; Ovary/metabolism ; Phenotype ; Progesterone/metabolism ; Proteomics ; Receptors, Nicotinic/metabolism ; alpha7 Nicotinic Acetylcholine Receptor/metabolism
Chemical Substances	Progesterone (4G7DS2Q64Y) ; Receptors, Nicotinic ; alpha7 Nicotinic Acetylcholine Receptor
Language	English
Publishing date	2023-08-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2034501-X
ISSN	1741-7899 ; 1470-1626 ; 1476-3990
ISSN (online)	1741-7899
ISSN	1470-1626 ; 1476-3990
DOI	10.1530/REP-23-0123
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Article ; Online: Structure of AMH bound to AMHR2 provides insight into a unique signaling pair in the TGF-β family.

Hart, Kaitlin N / Stocker, William A / Nagykery, Nicholas G / Walton, Kelly L / Harrison, Craig A / Donahoe, Patricia K / Pépin, David / Thompson, Thomas B

Proceedings of the National Academy of Sciences of the United States of America

2021 Volume 118, Issue 26

Abstract: Anti-Müllerian hormone (AMH), or Müllerian-inhibiting substance, is a protein hormone that promotes Müllerian duct regression during male fetal sexual differentiation and regulation of folliculogenesis in women. AMH is a member of the transforming growth ...

Abstract	Anti-Müllerian hormone (AMH), or Müllerian-inhibiting substance, is a protein hormone that promotes Müllerian duct regression during male fetal sexual differentiation and regulation of folliculogenesis in women. AMH is a member of the transforming growth factor beta (TGF-β) family, which has evolved to signal through its own dedicated type II receptor, AMH receptor type II (AMHR2). Structures of other TGF-β family members have revealed how ligands infer specificity for their cognate receptors; however, it is unknown how AMH binds AMHR2 at the molecular level. Therefore, in this study, we solved the X-ray crystal structure of AMH bound to the extracellular domain of AMHR2 to a resolution of 2.6Å. The structure reveals that while AMH binds AMHR2 in a similar location to Activin and BMP ligand binding to their type II receptors, differences in both AMH and AMHR2 account for a highly specific interaction. Furthermore, using an AMH responsive cell-based luciferase assay, we show that a conformation in finger 1 of AMHR2 and a salt bridge formed by K534 on AMH and D81/E84 of AMHR2 are key to the AMH/AMHR2 interaction. Overall, our study highlights how AMH engages AMHR2 using a modified paradigm of receptor binding facilitated by modifications to the three-finger toxin fold of AMHR2. Furthermore, understanding these elements contributing to the specificity of binding will help in the design of agonists or antagonists or the selection of antibody therapies.
MeSH term(s)	Activins/chemistry ; Amino Acid Sequence ; Anti-Mullerian Hormone/chemistry ; Anti-Mullerian Hormone/metabolism ; Bone Morphogenetic Proteins/chemistry ; Crystallography, X-Ray ; Models, Molecular ; Receptors, Peptide/chemistry ; Receptors, Peptide/metabolism ; Receptors, Transforming Growth Factor beta/chemistry ; Receptors, Transforming Growth Factor beta/metabolism ; Signal Transduction ; Structural Homology, Protein ; Transforming Growth Factor beta/metabolism
Chemical Substances	Bone Morphogenetic Proteins ; Receptors, Peptide ; Receptors, Transforming Growth Factor beta ; Transforming Growth Factor beta ; anti-Mullerian hormone receptor ; Activins (104625-48-1) ; Anti-Mullerian Hormone (80497-65-0)
Language	English
Publishing date	2021-06-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2104809118
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Article: Single-cell immunophenotyping of the fetal immune response to maternal SARS-CoV-2 infection in late gestation.

Matute, Juan / Finander, Benjamin / Pepin, David / Ai, Xinbin / Smith, Neal / Li, Jonathan / Edlow, Andrea / Villani, Alexandra / Lerou, Paul / Kalish, Brian

Research square

2021

Abstract: During the COVID-19 pandemic, thousands of pregnant women have been infected with SARS-CoV-2. The implications of maternal SARS-CoV-2 infection on fetal and childhood well-being are unknown. We aimed to characterize the fetal immune response to maternal ... ...

Abstract	During the COVID-19 pandemic, thousands of pregnant women have been infected with SARS-CoV-2. The implications of maternal SARS-CoV-2 infection on fetal and childhood well-being are unknown. We aimed to characterize the fetal immune response to maternal SARS-CoV-2 infection. We performed single-cell RNA sequencing and T-cell receptor (TCR) sequencing on cord blood mononuclear cells (CBMC) from newborns of mothers infected with SARS-CoV-2 in the third-trimester (cases) or without SARS-CoV-2 infection. We identified widespread gene expression changes in CBMC from cases, including upregulation of interferon-stimulated genes and Major Histocompatibility Complex genes in CD14 + monocytes; transcriptional changes suggestive of activation of plasmacytoid dendritic cells, and activation and exhaustion of NK cells and CD8 + T-cells. Lastly, we observed fetal TCR repertoire expansion in cases. As none of the infants were infected with SARS-CoV-2, our results suggest that SARS-CoV-2 maternal infection might modulate the fetal immune system in the absence of vertical transmission.
Language	English
Publishing date	2021-03-16
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-311000/v1
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