Stephen (He, Him) DiNardo
VerifiedUniversity of Pennsylvania · Rehabilitation Medicine
Active 1980–2025
About
Stephen (He, Him) DiNardo, Ph.D., is a Professor of Cell and Developmental Biology at the University of Pennsylvania's Perelman School of Medicine. He is a member of the Penn Institute for Regenerative Medicine (IRM) and specializes in studying adult stem cells within their natural environment, the niche, using Drosophila spermatogenesis as a model system. His research aims to uncover the general principles of stem cell regulation, focusing on niche-stem cell interactions, self-renewal, differentiation, proliferation, and stem cell aging. Dr. DiNardo's work involves applying genetic and genome-scale molecular approaches, high-resolution real-time imaging, and live imaging techniques to understand how niche cells are specified, assembled, and how they regulate stem cell behavior. His research extends to the morphogenesis of the niche, investigating how signaling pathways control the shape and behavior of niche cells and how cell biological responses are coordinated between niche and stem cells. His studies contribute to understanding tissue renewal and regenerative medicine, with a focus on the molecular mechanisms governing stem cell control and niche assembly in Drosophila, with implications for mammalian systems.
Research topics
- Computer Science
- Cell biology
- Operating system
- Biology
- Anatomy
Selected publications
bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-15
preprintOpen accessAbstract Stem cells require signals from a cellular microenvironment known as the niche that regulates identity, location, and division of stem cells. Niche cell identity must be properly specified during development to form a tissue capable of functioning in the adult. Here, we show that the Tbx1 ortholog org1 is expressed in Drosophila testis niche cells in response to Slit and FGF signals. org1 is expressed during niche development and is required to specify niche cell identity. org1 mutants specified fewer niche cells, and those cells showed disruption of niche-specific markers, including loss of the niche adhesion protein Fas3 and reduced hedgehog expression. We found that org1 expression in somatic gonadal precursors is capable of inducing formation of additional niche cells. Disrupted niche identity in org1 mutants resulted in niche assembly and functionality defects. We find the conserved transcription factor islet is expressed in response to org1 and show that islet functions downstream to mediate niche identity and assembly. This work identifies a novel role for org1 in niche establishment. Summary Statement Specification of niche identity is crucial to establish a functional stem cell microenvironment. Using a translatable model, we show that niche expression of org1 influences islet to specify niche identity.
2025-01-03
peer-reviewOpen accessSenior authorA new example of niche formation, revealing the mode of niche cell migration, implicates extrinsic sources of positional information, and uncovers the pathway required for stereotypical positioning of the niche.
eLife · 2025-01-03
articleOpen accessSenior authorNiches are often found in specific positions in tissues relative to the stem cells they support. Consistency of niche position suggests that placement is important for niche function. However, the complexity of most niches has precluded a thorough understanding of how their proper placement is established. To address this, we investigated the formation of a genetically tractable niche, the Drosophila Posterior Signaling Center (PSC), the assembly of which had not been previously explored. This niche controls hematopoietic progenitors of the lymph gland (LG). PSC cells were previously shown to be specified laterally in the embryo, but ultimately reside dorsally, at the LG posterior. Here, using live-imaging, we show that PSC cells migrate as a tight collective and associate with multiple tissues during their trajectory to the LG posterior. We find that Slit emanating from two extrinsic sources, visceral mesoderm and cardioblasts, is required for the PSC to remain a collective, and for its attachment to cardioblasts during migration. Without proper Slit-Robo signaling, PSC cells disperse, form aberrant contacts, and ultimately fail to reach their stereotypical position near progenitors. Our work characterizes a novel example of niche formation and identifies an extrinsic signaling relay that controls precise niche positioning.
Development · 2025-12-11
articleOpen accessStem cells require signals from a cellular microenvironment known as the niche that regulates identity, location and division of stem cells. Niche cell identity must be properly specified during development to form a tissue capable of functioning in the adult. Here, we show that the Tbx1 ortholog org-1 is expressed in Drosophila testis niche cells in response to Slit and FGF signals. org-1 is expressed during niche development and is required to specify niche cell identity. org-1 mutants specified fewer niche cells, and those cells showed disruption of niche-specific markers, including loss of the niche adhesion protein Fas3 and reduced hedgehog expression. We found that org-1 expression in somatic gonadal precursors is capable of inducing formation of additional niche cells. Disrupted niche identity in org-1 mutants caused defects in niche assembly and functionality. We found that the conserved transcription factor islet is expressed in response to org-1 and show that islet functions downstream to mediate niche identity and assembly. This work identifies a previously unreported role for org-1 in niche establishment.
An actomyosin network organizes niche morphology and responds to feedback from recruited stem cells
Current Biology · 2024-08-12 · 7 citations
articleOpen accessSenior authorbioRxiv (Cold Spring Harbor Laboratory) · 2024-06-25
preprintOpen accessSenior authorCorrespondingAbstract Niches are often found in specific positions in tissues relative to the stem cells they support. Consistency of niche position suggests that placement is important for niche function. However, the complexity of most niches has precluded a thorough understanding of how their proper placement is established. To address this, we investigated the formation of a genetically tractable niche, the Drosophila Posterior Signaling Center (PSC), the assembly of which had not been previously explored. This niche controls hematopoietic progenitors of the lymph gland (LG). PSC cells were previously shown to be specified laterally in the embryo, but ultimately reside dorsally, at the LG posterior. Here, using live-imaging, we show that PSC cells migrate as a tight collective and associate with multiple tissues during their trajectory to the LG posterior. We find that Slit emanating from two extrinsic sources, visceral mesoderm and cardioblasts, is required for the PSC to remain a collective, and for its attachment to cardioblasts during migration. Without proper Slit-Robo signaling, PSC cells disperse, form aberrant contacts, and ultimately fail to reach their stereotypical position near progenitors. Our work characterizes a novel example of niche formation and identifies an extrinsic signaling relay that controls precise niche positioning. Impact Statement A new example of niche formation is provided which reveals the mode of niche cell migration, implicates extrinsic sources that deliver positional information, and uncovers the signaling pathway required for the precise, stereotypical positioning of the niche.
eLife · 2024-08-27
articleOpen accessSenior authorNiches are often found in specific positions in tissues relative to the stem cells they support. Consistency of niche position suggests that placement is important for niche function. However, the complexity of most niches has precluded a thorough understanding of how their proper placement is established. To address this, we investigated the formation of a genetically tractable niche, the Drosophila Posterior Signaling Center (PSC), the assembly of which had not been previously explored. This niche controls hematopoietic progenitors of the lymph gland (LG). PSC cells were previously shown to be specified laterally in the embryo, but ultimately reside dorsally, at the LG posterior. Here, using live-imaging, we show that PSC cells migrate as a tight collective and associate with multiple tissues during their trajectory to the LG posterior. We find that Slit emanating from two extrinsic sources, visceral mesoderm and cardioblasts, is required for the PSC to remain a collective, and for its attachment to cardioblasts during migration. Without proper Slit-Robo signaling, PSC cells disperse, form aberrant contacts, and ultimately fail to reach their stereotypical position near progenitors. Our work characterizes a novel example of niche formation and identifies an extrinsic signaling relay that controls precise niche positioning.
2024-08-27
peer-reviewOpen accessSenior authorNiches are often found in specific positions in tissues relative to the stem cells they support. Consistency of niche position suggests that placement is important for niche function. However, the complexity of most niches has precluded a thorough understanding of how their proper placement is established. To address this, we investigated the formation of a genetically tractable niche, the Drosophila Posterior Signaling Center (PSC), the assembly of which had not been previously explored. This niche controls hematopoietic progenitors of the lymph gland (LG). PSC cells were previously shown to be specified laterally in the embryo, but ultimately reside dorsally, at the LG posterior. Here, using live-imaging, we show that PSC cells migrate as a tight collective and associate with multiple tissues during their trajectory to the LG posterior. We find that Slit emanating from two extrinsic sources, visceral mesoderm and cardioblasts, is required for the PSC to remain a collective, and for its attachment to cardioblasts during migration. Without proper Slit-Robo signaling, PSC cells disperse, form aberrant contacts, and ultimately fail to reach their stereotypical position near progenitors. Our work characterizes a novel example of niche formation and identifies an extrinsic signaling relay that controls precise niche positioning.A new example of niche formation is provided which reveals the mode of niche cell migration, implicates extrinsic sources that deliver positional information, and uncovers the signaling pathway required for the precise, stereotypical positioning of the niche.
Development · 2024-12-02 · 4 citations
articleOpen accessSenior authorStem cells are essential to repair and regenerate tissues, and often reside in a niche that controls their behavior. Here, we use the Drosophila testis niche, a paradigm for niche-stem cell interactions, to address the cell biological features that maintain niche structure and function during its steady-state operation. We report enrichment of Myosin II (MyoII) and a key regulator of actomyosin contractility (AMC), Rho Kinase (ROK), within the niche cell cortex at the interface with germline stem cells (GSCs). Compromising MyoII and ROK disrupts niche architecture, suggesting that AMC in niche cells is important to maintain its reproducible structure. Furthermore, defects in niche architecture disrupt GSC function. Our data suggest that the niche signals less robustly to adjacent germ cells yet permits increased numbers of cells to respond to the signal. Finally, compromising MyoII in niche cells leads to increased misorientation of centrosomes in GSCs as well as defects in the centrosome orientation checkpoint. Ultimately, this work identifies a crucial role for AMC-dependent maintenance of niche structure to ensure a proper complement of stem cells that correctly execute divisions.
eLife · 2024-08-27
preprintOpen accessSenior authorAbstract Niches are often found in specific positions in tissues relative to the stem cells they support. Consistency of niche position suggests that placement is important for niche function. However, the complexity of most niches has precluded a thorough understanding of how their proper placement is established. To address this, we investigated the formation of a genetically tractable niche, the Drosophila Posterior Signaling Center (PSC), the assembly of which had not been previously explored. This niche controls hematopoietic progenitors of the lymph gland (LG). PSC cells were previously shown to be specified laterally in the embryo, but ultimately reside dorsally, at the LG posterior. Here, using live-imaging, we show that PSC cells migrate as a tight collective and associate with multiple tissues during their trajectory to the LG posterior. We find that Slit emanating from two extrinsic sources, visceral mesoderm and cardioblasts, is required for the PSC to remain a collective, and for its attachment to cardioblasts during migration. Without proper Slit-Robo signaling, PSC cells disperse, form aberrant contacts, and ultimately fail to reach their stereotypical position near progenitors. Our work characterizes a novel example of niche formation and identifies an extrinsic signaling relay that controls precise niche positioning.
Recent grants
Control of Stem Cell Dynamics by a Niche at Steady-State and During Aging
NIH · $2.1M · 2020–2026
Stem Cell Renewal and Differentiation in Spermatogenesis
NIH · $6.9M · 1999–2021
NIH · $5.4M · 2014
Stem cell aging and the control of abscission
NIH · $1.2M · 2015–2021
Stem cell aging and the control of abscission
NIH · $440k · 2015–2017
Frequent coauthors
- 46 shared
Rolf Sternglanz
Nova Southeastern University
- 34 shared
K Voelkel
Karlsruhe Institute of Technology
- 24 shared
Lauren Anllo
University of Pennsylvania
- 21 shared
Kara A. Nelson
California Institute for Regenerative Medicine
- 16 shared
Kathleen Becherer
Sanford Burnham Prebys Medical Discovery Institute
- 16 shared
Louis A. Zumstein
University of Turin
- 14 shared
Kari F. Lenhart
Drexel University
- 14 shared
Erika Matunis
Johns Hopkins University
Labs
DiNardo LabPI
Education
- 1983
Ph.D., Biochemistry
Stony Brook University
Awards & honors
- Cert. 45 (Unconscious Bias for Leaders - Impact on Decision-…
- Cert. 30 (iCARE Training on Crisis Management) c 3a CAPS, Pe…
- Cert. 2e (Mentoring Facilitator for Faculty) c 2e CIMER, Uni…
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