The Human Cell Atlas (HCA) marks a decade of transforming how we understand human biology, with profound implications for regenerative medicine. In a recent thought leadership webinar, we interviewed Professor Fiona Watt of King’s College London and EMBL, who reflected on the journey of the HCA and its impact on tissue biology, disease research, and translational science.   The session, followed by a panel discussion moderated by Professor Watt, brought together leading experts Professor Maria Kasper(Karolinska Institutet) and Professor Karl Koehler (Harvard Medical School and Boston Children’s Hospital) to explore advances in spatial proteomics, single-cell transcriptomics, clinical translation, and the collaborative infrastructure shaping the future of tissue biology.  
 
Balancing Stem Cells and Differentiation 
 
Professor Watt’s career has centered on a fundamental biological principle: tissue health depends on balance. Rather than viewing stem cells as inherently “good” and differentiated cells as “bad,” her work emphasizes homeostasis — the dynamic equilibrium between renewal and specialization. 
 
In wound repair, this balance temporarily shifts toward stem cell expansion before restoring normal tissue structure. In inflammatory diseases such as psoriasis, targeted biologic therapies can reestablish equilibrium. Cancer, however, represents a more complex breakdown of this balance. In squamous cell carcinomas, tumor grading still reflects the proportion of differentiated cells — the closer the tumor resembles normal tissue, the better the prognosis. 
 
These insights have shaped regenerative medicine’s understanding that successful therapies must restore balance, not simply increase stem cell numbers. 
 
Restoring Balance: The Core Principle of Regenerative Medicine
 
Professor Watt’s scientific career has focused on a fundamental concept: tissue health depends on balance. Stem cells and differentiated cells exist in dynamic equilibrium, maintaining homeostasis in adult tissues. 
 
In wound healing, stem cell expansion is temporarily increased before differentiation restores structure. In inflammatory diseases such as psoriasis, therapeutic interventions can normalize disrupted balance. In cancer — particularly squamous cell carcinomas — this equilibrium becomes more complex, with tumor grading still reflecting the proportion of differentiated cells. 
 
Rather than simply promoting stem cell expansion, regenerative medicine must restore this delicate balance. 
 
From Single Cells to Global Infrastructure 
 
Professor Watt was present at the launch of the Human Cell Atlas a decade ago, recognizing early the promise of single-cell RNA sequencing. What began as technically limited single-cell experiments has evolved into a global scientific infrastructure. 
 
Today, the HCA comprises 18 biological networks and nearly 200 published studies, shifting from static cell catalogs toward connected, semi-global references spanning development, immunity, and barrier tissues such as skin. 
 
Importantly, the field has moved beyond asking “What cell types exist?” to “How do cell states function, interact, and change?” 
 
Skin Biology: Diversity in Context 
 
Through her lab’s contributions to comprehensive skin atlases across development, adulthood, and inflammatory disease, Professor Watt highlighted a key insight: most tissues do not harbor entirely new cell types across anatomical sites — instead, cell abundance and state vary. 
 
In basal cell carcinoma, for example, cancer-associated fibroblasts were shown to represent expansions of pre-existing populations rather than novel cell types. Meanwhile, immune cell diversity across tissues has emerged as central to understanding both regeneration and pathology. 
 
Yet single-cell data also raise new questions. While transcriptional heterogeneity is visible, interpreting its functional meaning remains one of the field’s biggest challenges. 
 
Advances in Spatial Proteomics and Transcriptomics 
 
The panel discussion emphasized how spatial technologies are redefining tissue analysis. 
 
Spatial transcriptomics and multiplexed in situ approaches overcome biases introduced by tissue dissociation, revealing cell populations that may otherwise be underrepresented. New high-plex imaging platforms allow researchers to interrogate over 100 markers within a single tissue section, integrating cell identity with anatomical context.
 
These advances are transforming the Human Cell Atlas from a list of cell types into a functional tissue map. 
 
Organoids and Regenerative Applications 
 
Professor Karl Koehler — Associate Professor of Otolaryngology–Head and Neck Surgery at Harvard Medical School and Principal Investigator at Boston Children’s Hospital — discussed how organoid systems are being guided by HCA reference data. 
 
Complex skin and inner ear organoids derived from pluripotent stem cells now model development and disease with increasing fidelity. While clinical translation remains challenging, stem-cell derived therapies for diabetes and Parkinson’s disease signal that regenerative medicine is entering a new phase. 
 
Organoid systems also provide platforms for gene therapy testing in congenital disorders such as epidermolysis bullosa and Usher syndrome. 
 
Data Integration: The Persistent Bottleneck 
 
Despite extraordinary progress, data integration remains difficult. 
 
Professor Maria Kasper — Professor of Cell and Molecular Biology at Karolinska Institutet — noted challenges in harmonizing metadata, regulatory barriers to raw data sharing across countries, and inconsistent annotation practices in earlier studies. 
 
The HCA is working toward structured data portals and shared nomenclature frameworks, but building a “living reference atlas” that evolves with new data requires both technical and cultural shifts. 
 
The question moving forward is whether the Atlas should remain a static reference or become a dynamic, continuously updated biological model. 
 
Challenges in Clinical Development 
 
Bringing single-cell and spatial technologies into clinical practice demands regulatory rigor, validation standards, and scalable workflows.
 
One promising direction involves applying AI to archived pathology slides, enabling insights from HCA research to inform decades-old tissue samples. If successful, this could bridge discovery science and routine diagnostics. 
 
However, as panelists emphasized, translating regenerative approaches — particularly complex organoid-based therapies — requires sustained investment and long-term commitment. 
 
Leadership and Scientific Equity 
 
Beyond laboratory science, Professor Watt’s leadership roles — including former Executive Chair of the UK Medical Research Council and current EMBO Director — reflect her commitment to strengthening research ecosystems. 
 
From supporting clinician-scientists to promoting equitable opportunities across Europe, she underscored that scientific excellence can emerge anywhere, given the right infrastructure and collaboration. 
 
Looking Ahead 
 
The next decade of regenerative medicine will require integrating cell type, spatial location, and functional behavior into cohesive models of tissue biology. 
 
If the first ten years of the Human Cell Atlas were about mapping, the next ten will be about application — translating cellular insight into therapies that restore balance, repair tissues, and improve human health.